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Sample records for cell accumulation histamine

  1. Histamine prevents polyamine accumulation in mouse C57.1 mast cell cultures.

    Science.gov (United States)

    Fajardo, I; Urdiales, J L; Paz, J C; Chavarría, T; Sánchez-Jiménez, F; Medina, M A

    2001-02-01

    The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line (C57.1), as a cell model in which both biogenic amines are important for maintaining cell function and viability. Results obtained after incubations with exogenous histamine indicated that histamine prevents polyamine accumulation by affecting polyamine uptake. A plasma membrane transport system for polyamines has been also studied in mast cells. It seems to be a Na(+)-dependent uptake with high affinity for both spermine and spermidine and lower affinity for putrescine and agmatine. Polyamine uptake was reduced in both cells treated with exogenous histamine and histamine-preloaded cells. However, ornithine decarboxylase activity and cell proliferation were not affected by histamine. Incubation with histamine enhanced the spermidine/spermine acetyl transferase induction caused by N(1)-ethyl-N(11)-[(cyclopropyl)methyl]-4,8-diazaundecane, suggesting that polyamine acetylation could be another mechanism by which histamine prevents polyamine accumulation in C57.1 mast cells.

  2. Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

    Directory of Open Access Journals (Sweden)

    Mo Ya-Zhen

    2009-04-01

    Full Text Available Abstract Background It has been recognized that phospholipase A2 (PLA2 is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA2 provoke inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops mucrosquamatus crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation. Results The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation. Conclusion TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation.

  3. Physiological significance of ECL-cell histamine.

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    Andersson, K.; Chen, D.; Mattsson, H.; Sundler, F.; Håkanson, R.

    1998-01-01

    In the oxyntic mucosa of the mammalian stomach, histamine is stored in ECL cells and in mucosal mast cells. In the rat, at least 80 percent of oxyntic mucosal histamine resides in the ECL cells. Histamine is a key factor in the regulation of gastric acid secretion. Following depletion of ECL-cell histamine by treatment with alpha-fluoromethylhistidine (alpha-FMH), basal acid secretion was reduced, and gastrin-stimulated acid secretion was abolished. Vagally-induced acid secretion (by insulin ...

  4. Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors.

    OpenAIRE

    Sedor, J R; Abboud, H E

    1985-01-01

    Histamine influences the glomerular microcirculation and modulates immune-inflammatory responses. In the rat kidney, histamine is synthesized by glomeruli and stimulates cyclic nucleotide production specifically in glomeruli. We investigated the in vitro effect of histamine on cyclic nucleotide accumulation in rat cultured glomerular mesangial and epithelial cells. Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein,...

  5. Histamine regulates murine primary dendritic cell functions.

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    Schenk, Heiko; Neumann, Detlef; Kloth, Christina

    2016-10-01

    The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs. DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry. Individual contributions of the histamine receptor subtypes were determined by using the antagonists mepyramine (histamine H1-receptor: H1R), famotidine (H2R), and JNJ 7777120 (H4R). Histamine accelerated the uptake of soluble antigen via the H1R, H2R, and H4R in splenic DCs. Co-stimulatory molecule expression was enhanced already by enrichment procedures, thus, the analyses were performed in unseparated cell populations. Histamine enhanced the expression of CD86 and ICOS-L while expression of CD80 was unaffected. Antagonism at H1R, H2R, and H4R and at H1R and H4R reduced the histamine-induced enhanced expression of CD86 and ICOS-L, respectively. Histamine contributes to the regulation of the immunological synapse by stimulation of antigen uptake and activation of DCs via H1R, H2R, and H4R.

  6. Histamine Release from Mast Cells and Basophils.

    Science.gov (United States)

    Borriello, Francesco; Iannone, Raffaella; Marone, Gianni

    2017-01-01

    Mast cells and basophils represent the most relevant source of histamine in the immune system. Histamine is stored in cytoplasmic granules along with other amines (e.g., serotonin), proteases, proteoglycans, cytokines/chemokines, and angiogenic factors and rapidly released upon triggering with a variety of stimuli. Moreover, mast cell and basophil histamine release is regulated by several activating and inhibitory receptors. The engagement of different receptors can trigger different modalities of histamine release and degranulation. Histamine released from mast cells and basophils exerts its biological activities by activating four G protein-coupled receptors, namely H1R, H2R, H3R (expressed mainly in the brain), and the recently identified H4R. While H1R and H2R activation accounts mainly for some mast cell- and basophil-mediated allergic disorders, the selective expression of H4R on immune cells is uncovering new roles for histamine (possibly derived from mast cells and basophils) in allergic, inflammatory, and autoimmune disorders. Thus, the in-depth knowledge of mast cell and basophil histamine release and its biologic effects is poised to uncover new therapeutic avenues for a wide spectrum of disorders.

  7. Autoregulation of enterochromaffin-like cell histamine secretion via the histamine 3 receptor subtype.

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    Kidd, M.; Tang, L. H.; Miu, K.; Lawton, G. P.; Sandor, A.; Modlin, I. M.

    1996-01-01

    INTRODUCTION: The neuroendocrine histamine-secreting cell of the gastric fundus, the enferochromaffin-like cell, is the principal regulator of parietal cell acid secretion. We have proposed that histamine may regulate its own synthesis and release via an autocrine mechanism. The purpose of this study was to evaluate the role of the histamine receptor subtypes H1, H2 and H3 in the regulation of this phenomenon. METHODS: Purified ECL cells were isolated by pronase digestion and EDTA exposure of...

  8. Homologous desensitization of histamine-mediated signal transduction system in C6 glioma cells.

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    Tseng, Chin-Lu; Wei, Jiann-Wu

    2013-04-30

    Molecular events involved in the homologous desensitization of histamine-mediated signal transduction system in glioma cells are not well understood. The aim of this study was designed to gain further insight into possible events in the process using the C6 glioma cells. Incubation of histamine caused increases in inositol phosphate (IP1) formation and intracellular free-calcium concentration [Ca2+]i in C6 glioma cells via the activation of a G-protein-coupled phospholipase C (PI-PLC). Histamine also caused an increase in extracellular release of arachidonic acid (AA) and formation of glycerophosphoinositol (GPI). These effects are likely to be mediated through the activation of receptor-coupled phospholipase A2 (PLA2). Pretreatment of C6 cells with histamine, from 0.1 microM to 1 mM concentrations, for 10 to 60 min significantly reduced the histamine-induced IP1 production, [Ca2+]i accumulation, AA release and GPI formation, despite repeated wash of the cells with buffer solution. Staurosporine (10 nM), a protein kinase C (PKC) inhibitor, reversed almost completely IP1 production, or partially for [Ca2+]i, GPI formation and AA release of this homologous desensitization effect of histamine. Pretreatment of C6 cells with phorbol 12-myristate 13-acetate (PMA), a PKC activator, at 0.1 nM to 0.1 microM for 2 to 15 min caused a reduction of histamine-induced IP1 formation and [Ca2+] accumulation, but enhanced histamine-induced AA release and GPI formation. Ten nM staurosporine completely reversed the effect of PMA on histamine-induced IP1 formation and partially on [Ca2+]i accumulation. However, staurosporine potentiated the effect of PMA on histamine-induced AA release and GPI formation, but the effect could be blocked by H7, a calcium-dependent PKC inhibitor. Our results indicate that activation of PKC by histamine in the signal transduction system is involved in the histamine-induced homologous desensitization event. Since PMA pretreatment could not mimic histamine

  9. Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

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    DeVries, Zachary C; Santangelo, Richard G; Barbarin, Alexis M; Schal, Coby

    2018-01-01

    Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean emergent contaminant and pose a serious health risk in the indoor environment.

  10. Mast cell-derived histamine mediates cystitis pain.

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    Charles N Rudick

    2008-05-01

    Full Text Available Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC.Infection of mice with pseudorabies virus (PRV induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF, TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology.These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.

  11. Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

    Directory of Open Access Journals (Sweden)

    Zachary C DeVries

    Full Text Available Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust. Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment.

  12. Aortic endothelial and smooth muscle histamine metabolism. Relationship to aortic 125I-albumin accumulation in experimental diabetes

    International Nuclear Information System (INIS)

    Hollis, T.M.; Gallik, S.G.; Orlidge, A.; Yost, J.C.

    1983-01-01

    We studied rat aortic endothelial and smooth muscle cell de novo histamine synthesis mediated by histidine decarboxylase (HD) and the effects of its inhibition by alpha-hydrazinohistidine on the intracellular histamine content and intraaortic albumin accumulation in streptozotocin-induced diabetes. Diabetes was induced by a single jugular vein injection of streptozotocin (60 mg/kg, pH 4.5, ether anesthesia), with animals held 4 weeks following the overt manifestation of diabetes. Additional diabetic and nondiabetic rats received alpha-hydrazinohistidine (25 mg/kg, i.p. every 12 hours) during the last week; this had no effect on the severity of diabetes in any animal receiving streptozotocin. Data indicate that the aortic endothelial (EC) HD activity was increased more than 130% in the untreated diabetic group but was similar to control values in the diabetic group receiving alpha-hydrazinohistidine; similarily, the EC histamine content from diabetic aortas increased 127% over control values, but in EC from diabetic animals receiving alpha-hydrazinohistidine it was comparable to control values. Similar trends were observed for the subjacent aortic smooth muscle. In untreated diabetic animals the aortic 125I-albumin mass transfer rate was increased 60% over control values, while in diabetic animals receiving alpha-hydrazinohistidine the 125I-albumin mass transfer rate was essentially identical to controls. These data indicate that in streptozotocin diabetes there is an expansion of the inducible aortic histamine pool, and that this expansion is intimately related to the increased aortic albumin accumulation

  13. Control of tyramine and histamine accumulation by lactic acid bacteria using bacteriocin forming lactococci.

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    Tabanelli, Giulia; Montanari, Chiara; Bargossi, Eleonora; Lanciotti, Rosalba; Gatto, Veronica; Felis, Giovanna; Torriani, Sandra; Gardini, Fausto

    2014-11-03

    The aim of this study was to evaluate the competitive effects of three bacteriocin producing strains of Lactococcus lactis subsp. lactis against two aminobiogenic lactic acid bacteria, i.e. the tyramine producing strain Enterococcus faecalis EF37 and the histamine producing strain Streptococcus thermophilus PRI60, inoculated at different initial concentrations (from 2 to 6 log cfu/ml). The results showed that the three L. lactis subsp. lactis strains were able to produce bacteriocins: in particular, L. lactis subsp. lactis VR84 and EG46 produced, respectively, nisin Z and lacticin 481, while for the strains CG27 the bacteriocin has not been yet identified, even if its peptidic nature has been demonstrated. The co-culture of E. faecalis EF37 in combination with lactococci significantly reduced the growth potential of this aminobiogenic strain, both in terms of growth rate and maximum cell concentration, depending on the initial inoculum level of E. faecalis. Tyramine accumulation was strongly reduced when E. faecalis EF37 was inoculated at 2 log cfu/ml and, to a lesser extent, at 3 log cfu/ml, as a result of a lower cell load of the aminobiogenic strain. All the lactococci were more efficient in inhibiting streptococci in comparison with E. faecalis EF37; in particular, L. lactis subsp. lactis VR84 induced the death of S. thermophilus PRI60 and allowed the detection of histamine traces only at higher streptococci inoculum levels (5-6 log cfu/ml). The other two lactococcal strains did not show a lethal action against S. thermophilus PRI60, but were able to reduce its growth extent and histamine accumulation, even if L. lactis subsp. lactis EG46 was less effective when the initial streptococci concentration was 5 and 6 log cfu/ml. This preliminary study has clarified some aspects regarding the ratio between bacteriocinogenic strains and aminobiogenic strains with respect to the possibility to accumulate BA and has also showed that different bacteriocins can have

  14. Mast cell and histamine content of human bronchoalveolar lavage fluid.

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    Agius, R M; Godfrey, R C; Holgate, S T

    1985-01-01

    Bronchoalveolar lavage was performed in 97 patients including control patients with bronchial carcinoma (24) and patients with sarcoidosis (20), cryptogenic fibrosing alveolitis (9), and asthma (4), and others. Cytocentrifuged slides were stained by two methods: May-Grünwald Giemsa and toluidine blue. In the last 32 subjects the bronchoalveolar lavage fluid was separated into supernatant and cell pellet for the subsequent assay of the performed mast cell mediator, histamine. Comparison of the two methods of staining showed a bias towards toluidine blue. Controls had a differential mean (SE) mast cell count of 0.07% (0.01%). Higher counts were noted in cryptogenic fibrosing alveolitis--0.61% (0.15%) (p less than 0.001)--and in sarcoidosis--0.14% (0.02%) (p less than 0.05). There was a strong correlation between absolute mast cell counts and cell lysate histamine concentration (r = 0.78, p less than 0.001). Less strong, significant, correlations between supernatant histamine concentration and absolute mast cell counts (r = 0.48, p less than 0.01) or cell lysate histamine concentration (r = 0.72, p less than 0.01) were also found. Derived mean values of histamine per mast cell ranged from 3.7 to 10.9 picograms. The mean histamine content of lavage fluid supernatant as a percentage of the total lavage fluid histamine was 24.9% (3.3%). The possible clinical significance of these findings is discussed. Images PMID:4060097

  15. Histamine receptor 2 modifies dendritic cell responses to microbial ligands.

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    Frei, Remo; Ferstl, Ruth; Konieczna, Patrycja; Ziegler, Mario; Simon, Tunde; Rugeles, Tulia Mateus; Mailand, Susanne; Watanabe, Takeshi; Lauener, Roger; Akdis, Cezmi A; O'Mahony, Liam

    2013-07-01

    The induction of tolerance and protective immunity to microbes is significantly influenced by host- and microbiota-derived metabolites, such as histamine. We sought to identify the molecular mechanisms for histamine-mediated modulation of pattern recognition receptor signaling. Human monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells, and plasmacytoid dendritic cells were examined. Cytokine secretion, gene expression, and transcription factor activation were measured after stimulation with microbial ligands and histamine. Histamine receptor 2 (H₂R)-deficient mice, histamine receptors, and their signaling pathways were investigated. Histamine suppressed MDDC chemokine and proinflammatory cytokine secretion, nuclear factor κB and activator protein 1 activation, mitogen-activated protein kinase phosphorylation, and T(H)1 polarization of naive lymphocytes, whereas IL-10 secretion was enhanced in response to LPS and Pam3Cys. Histamine also suppressed LPS-induced myeloid dendritic cell TNF-α secretion and suppressed CpG-induced plasmacytoid dendritic cell IFN-α gene expression. H₂R signaling through cyclic AMP and exchange protein directly activated by cyclic AMP was required for the histamine effect on LPS-induced MDDC responses. Lactobacillus rhamnosus, which secretes histamine, significantly suppressed Peyer patch IL-2, IL-4, IL-5, IL-12, TNF-α, and GM-CSF secretion in wild-type but not H₂R-deficient animals. Both host- and microbiota-derived histamine significantly alter the innate immune response to microbes through H₂R. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2.

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    Simon, Tünde; Gogolák, Péter; Kis-Tóth, Katalin; Jelinek, Ivett; László, Valéria; Rajnavölgyi, Eva

    2012-02-01

    Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a(-) and CD1a(+) monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific manner. Histamine shifts DC differentiation to the development of CD1a(-) DCs and modulates DC activation through its inhibitory effect on CD1a(+) DC differentiation. Histamine-induced reduction of CD1a(+) DCs is associated with increased secretion of IL-6 and IL-10, up-regulation of a typical combination of chemokines, expression C5aR1 by the CD1a(-) DC subset and enhanced migration of both activated DC subsets supported by the production of MMP-9 and MMP-12 enzymes. All these effects were shown to be mediated in a H2R-specific manner as revealed by the specific antagonist of the receptor. As H2R is expressed at high levels in both DC subsets, we propose that it may dominate the regulation of multiple DC functions. In contrast, H1R and H4R with opposing subset-related expression may have a regulatory or fine-tuning role in histamine-induced functional activities.

  17. A method for production and determination of histamine releasing activity from human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Kampen, G T; Poulsen, L K; Reimert, C M

    1997-01-01

    Histamine releasing factors, i.e. cytokines capable of inducing histamine release from basophils or mast cells, have been suggested to be involved in the pathogenesis of, for example, allergic late-phase reactions. Here we describe a controlled method for production and determination of histamine......). The preparations of HRA induced dose- and Ca2+-dependent histamine release from leukocytes. Supernatants of parallel cultures of unstimulated MNC did not induce histamine release. The HRA was neither due to exogenous histamine releasing compounds (e.g. Con A) nor to residual histamine in the preparations of HRA....... The kinetics of HRA induced histamine release (half-maximal release after > 40 min) were slower and more protracted than those of anti-IgE induced histamine release. However, based on a comparison between HRA induced histamine release from leukocytes and purified (97%) basophils, this did not appear to be due...

  18. Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to Ca2+ mobilization and cell proliferation.

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    Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Certal, Mariana; Costa, Maria Adelina; Costa, Cristina; Magalhães-Cardoso, Maria Teresa; Ferreirinha, Fátima; Sévigny, Jean; Correia-de-Sá, Paulo

    2013-09-20

    Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca(2+) ([Ca(2+)]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca(2+)]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca(2+)]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with (10)Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca(2+)]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.

  19. Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+ Mobilization and Cell Proliferation*

    Science.gov (United States)

    Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Certal, Mariana; Costa, Maria Adelina; Costa, Cristina; Magalhães-Cardoso, Maria Teresa; Ferreirinha, Fátima; Sévigny, Jean; Correia-de-Sá, Paulo

    2013-01-01

    Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca2+ ([Ca2+]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca2+]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca2+]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with 10Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca2+]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca2+]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors. PMID:23918924

  20. Measuring histamine and cytokine release from basophils and mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

    2014-01-01

    Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ s...

  1. The Effect of Histamine on Inward and Outward Currents in Mouse Retinal Amacrine Cells.

    Science.gov (United States)

    Horio, Kayo; Ohkuma, Mahito; Miyachi, Ei-Ichi

    2018-04-01

    The expression of H1 receptor has been reported in amacrine cells of mouse and rat retinae. However, we assumed that other types of histamine receptors also function in amacrine cells. In order to confirm that histamine modulates the membrane potential in mouse amacrine cells, we measured voltage-gated currents using whole-cell configuration. Under voltage-clamp conditions, the amplitude of voltage-gated outward currents was enhanced by the application of 100 µM histamine in 65% of amacrine cells. Histamine also increased the amplitudes of voltage-gated inward currents in 72% of amacrine cells. When antagonists of the histamine H1, H2, or H3 receptors were applied to histamine-sensitive amacrine cells, all three types of these inhibitors reduced the effect of histamine. Moreover, we classified recorded cells into seven types based on their morphological characteristics. Two of the seven types, diffuse multistratified cells and AII amacrine cells, responded significantly to histamine. These results indicate that histamine affected the membrane potential via three types of histamine receptors. Furthermore, there were differences in the responses to histamine among types of amacrine cells. Histamine may be one of the important neurotransmitters and/or neuromodulators in the visual processing.

  2. Effects of inoculation of commercial starter cultures on the quality and histamine accumulation in fermented sausages.

    Science.gov (United States)

    Wang, Xinhui; Ren, Hongyang; Wang, Wei; Zhang, Yin; Bai, Ting; Li, Junxia; Zhu, Wenyou

    2015-02-01

    To meet the requirements of high-quality safe products, starter cultures are used to produce fermented sausages. The effects of 3 commercial starter cultures, namely SM-194, T-SPX, and SM-181, on histamine accumulation and quality parameters including microbial quality, pH, water activity, and total volatile base nitrogen, as well as the color and texture properties, were evaluated during the fermentation and ripening of fermented sausages. Although initial counts of Escherichia coli, Enterobacteriaceae, and Pseudomonas were similar in the 4 batches, the growth of these microorganisms was significantly inhibited (P sausages, respectively. At the end of ripening, the levels of histamine were 8.85, 0.32, 7.82, and 3.18 mg/kg for batches C, SM-194, T-SPX, and SM-181, respectively. The results revealed that commercial starter cultures, particularly starter cultures SM-194 and SM-181, made a great contribution to histamine reduction. In addition, batches inoculated with starter cultures showed a stronger acidification and lower level of total volatile base nitrogen than the control sample during production (P sausages. © 2015 Institute of Food Technologists®

  3. Interactions between accumulated copper, bacterial community structure and histamine levels in crayfish meat during storage.

    Science.gov (United States)

    Soedarini, Bernadeta; van Gestel, Cornelis A M; van Straalen, Nico M; Widianarko, Budi; Röling, Wilfred F M

    2014-08-01

    Pollution in aquaculture areas may negatively impact edible species and threaten seafood quality and safety. The aim of this study was to determine the interaction between copper and bacteria in the aquatic habitat and their impact upon crustaceans. Marbled crayfish was chosen as a model of aquatic crustaceans and the influence of metal contamination on bacterial community structure in water used to culture crayfish and in crayfish themselves was investigated. Histamine, an allergen commonly formed by certain groups of bacteria in crustacean edible tissue during storage, was also determined. Copper exposure increased its concentration in crayfish meat by 17.4%, but the copper concentration remained within acceptable food safety limits. Elevated copper levels affected the bacterial community both in the water used to cultivate crayfish and in the marbled crayfish themselves. Cluster analysis of 16S rRNA-gene based microbial community fingerprints revealed that copper impacted the bacterial community in the water and in the crayfish meat. However, copper exposure reduced the formation of histamine in crayfish meat during storage by 66.3%. Copper from the habitat appears to reduce histamine accumulation in crayfish meat during storage by affecting the bacterial community structure of the cultivation water and most likely also in the intestine of the crayfish. From a food safety point of view, copper treatment during the aqua culturing of crustaceans has a positive impact on the postharvest stage. © 2013 Society of Chemical Industry.

  4. Histamine Stimulates Hydrogen Peroxide Production by Bronchial Epithelial Cells via Histamine H1 Receptor and Dual Oxidase

    Science.gov (United States)

    Rada, Balázs; Boudreau, Howard E.; Park, Jonathan J.

    2014-01-01

    Oxidative stress has been implicated in the pathogenesis of bronchial asthma. Besides granulocytes, the airway epithelium can produce large amounts of reactive oxygen species and can contribute to asthma-related oxidative stress. Histamine is a major inflammatory mediator present in large quantities in asthmatic airways. Whether histamine triggers epithelium-derived oxidative stress is unknown. We therefore aimed at characterizing human airway epithelial H2O2 production stimulated by histamine. We found that air–liquid interface cultures of primary human bronchial epithelial cells (BECs) and an immortalized BEC model (Cdk4/hTERT HBEC) produce H2O2 in response to histamine. The main source of airway epithelial H2O2 is an NADPH dual oxidase, Duox1. Out of the four histamine receptors (H1R–H4R), H1R has the highest expression in BECs and mediates the H2O2–producing effects of histamine. IL-4 induces Duox1 gene and protein expression levels and enhances histamine-induced H2O2 production by epithelial cells. Using HEK-293 cells expressing Duox1 or Duox2 and endogenous H1R, histamine triggers an immediate intracellular calcium signal and H2O2 release. Overexpression of H1R further increases the oxidative output of Duox-expressing HEK-293 cells. Our observations show that BECs respond to histamine with Duox-mediated H2O2 production. These findings reveal a mechanism that could be an important contributor to oxidative stress characteristic of asthmatic airways, suggesting novel therapeutic targets for treating asthmatic airway disease. PMID:23962049

  5. Histamine downregulates aquaporin 5 in human nasal epithelial cells.

    Science.gov (United States)

    Wang, Weiwei; Wang, Xiaolian; Ma, Lan; Zhang, Ruitao

    2015-01-01

    Aquaporin 5 (AQP5) is a water-specific channel protein. It is thought to be a key participant in fluid secretion and a rate-limiting barrier to the secretion seen during allergic inflammation. We sought to determine the effect of histamine on AQP5 expression in human nasal epithelial cells (HNEpC). HNEpC cells were cultured with four concentrations of histamine in vitro. The phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (CREB) at serine 133 and the AQP5 protein were measured by using immunocytochemistry and Western blotting. Real-time polymerase chain reaction was used to detect AQP5 messenger ribonucleic acid (mRNA). Concentration-dependent histamine induced-inhibition of CREB phosphorylation at serine 133 in HNEpC cells was observed, and AQP5 mRNA and protein were also downregulated in a concentration-dependent fashion. Histamine downregulates AQP5 production in HNEpC cells by inhibiting CREB phosphorylation at serine 133.

  6. Role of histamine and its receptor subtypes in stimulation of conjunctival goblet cell secretion.

    Science.gov (United States)

    Hayashi, Densen; Li, Dayu; Hayashi, Chisato; Shatos, Marie; Hodges, Robin R; Dartt, Darlene A

    2012-05-17

    The purpose of this study was to determine the effect of histamine and its receptors on goblet cell secretion. Cultured rat and human goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugate was measured by an enzyme-linked lectin assay. Cultured rat goblet cells were homogenized and either RNA was isolated for RT-PCR or proteins were isolated for Western blot analysis for presence of histamine receptors subtypes H₁ through H₄. The localization of these receptors was determined in rat and human goblet cells by immunofluorescence microscopy. Histamine stimulated goblet cell secretion in a concentration- and time-dependent manner. All four histamine receptors were present in cultured rat and human goblet cells. Use of agonists specific to individual histamine receptor subtypes indicated that the rank order of agonist stimulation was H₁ = H₃ > H₄ > H₂. Using antagonists specific to individual histamine receptor subtypes determined that H₂ and H₃, but not the H₁ and H₄, antagonists, inhibited histamine-stimulated conjunctival goblet cell secretion. Rat and human conjunctival goblet cells are a direct target of histamine, which induces secretion. All four histamine receptors are present in rat and human conjunctiva and are active in rat conjunctival goblet cells. These findings suggest that all four histamine receptor subtypes are important for conjunctival goblet cell secretion. Blockage of histamine receptor subtypes could prevent the excess mucus production associated with ocular allergy.

  7. Histamine via the histamine H₂-receptor reduces α-CD3-induced interferon-γ synthesis in murine CD4+ T cells in an indirect manner.

    Science.gov (United States)

    Vauth, Marcus; Möhner, Desirée; Beermann, Silke; Seifert, Roland; Neumann, Detlef

    2012-04-01

    Histamine is involved in the execution of an immune reaction. Receptors for histamine, of which four different subtypes are known so far, are found on dendritic cells and on T cells. Via these receptors, histamine either indirectly or directly affects the activation of T cells. Data in the literature regarding the involved receptor subtypes and the mode of action of histamine on T cells are somewhat contradictory and depend on the type of cells analyzed, polarized T cells, or freshly prepared T cells within the context of the whole splenocyte population. Therefore, we analyzed the effect of histamine on murine T cells within splenocytes in a detailed manner. We stimulated freshly prepared splenocytes in the presence or absence of histamine with α-CD3 in vitro and analyzed the induced cytokine production. We show that histamine reduced the α-CD3-induced interferon-γ (IFN-γ) production of CD4⁺ cells via the histamine H₂-receptor. Moreover, the effect of histamine on the α-CD3-induced IFN-γ production could be transferred within conditioned splenocyte supernatants induced by histamine (in the absence of α-CD3). Thus, the histamine effect is mediated by a soluble factor, which, however, is neither of the classical anti-inflammatory mediators, interleukin-10, or transforming growth factor-β.

  8. Rapid desensitization of the histamine H2 receptor on the human monocytic cell line U937

    NARCIS (Netherlands)

    Smit, M J; Leurs, R; Shukrula, S R; Bast, A; Timmerman, H

    1994-01-01

    In the present study we have subjected the histamine H2 receptor on the monocytic cell line U937 to a thorough pharmacological characterization using a series of selective histamine H1, H2 and H3 receptor agonists and antagonists. Recent reports have demonstrated the existence of a histamine H2

  9. Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists.

    OpenAIRE

    Van der Ven, L. T.; Prinsen, I. M.; Jansen, G. H.; Roholl, P. J.; Defferrari, R.; Slater, R.; Den Otter, W.

    1993-01-01

    The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures. Twelve freshly excised human gliomas were cultured and tested for thei...

  10. Polyamines affect histamine synthesis during early stages of IL-3-induced bone marrow cell differentiation.

    Science.gov (United States)

    García-Faroldi, Gianni; Correa-Fiz, Florencia; Abrighach, Hicham; Berdasco, María; Fraga, Mario F; Esteller, Manel; Urdiales, José L; Sánchez-Jiménez, Francisca; Fajardo, Ignacio

    2009-09-01

    Mast cells synthesize and store histamine, a key immunomodulatory mediator. Polyamines are essential for every living cell. Previously, we detected an antagonistic relationship between the metabolisms of these amines in established mast cell and basophilic cell lines. Here, we used the IL-3-driven mouse bone marrow-derived mast cell (BMMC) culture system to further investigate this antagonism in a mast cell model of deeper physiological significance. Polyamines and histamine levels followed opposite profiles along the bone marrow cell cultures leading to BMMCs. alpha-Difluoromethylornithine (DFMO)-induced polyamine depletion resulted in an upregulation of histidine decarboxylase (HDC, the histamine-synthesizing enzyme) expression and activity, accompanied by increased histamine levels, specifically during early stages of these cell cultures, where an active histamine synthesis process occurs. In contrast, DFMO did not induce any effect in either HDC activity or histamine levels of differentiated BMMCs or C57.1 mast cells, that exhibit a nearly inactive histamine synthesis rate. Sequence-specific DNA methylation analysis revealed that the DFMO-induced HDC mRNA upregulation observed in early bone marrow cell cultures is not attributable to a demethylation of the gene promoter caused by the pharmacological polyamine depletion. Taken together, the results support an inverse relationship between histamine and polyamine metabolisms during the bone marrow cell cultures leading to BMMCs and, moreover, suggest that the regulation of the histamine synthesis occurring during the early stages of these cultures depends on the concentrations of polyamines. (c) 2009 Wiley-Liss, Inc.

  11. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line

    Science.gov (United States)

    Wang, Yi; Jiang, Yang; Ikeda, Jun-ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-01-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine. PMID:25045085

  12. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line.

    Science.gov (United States)

    Wang, Yi; Jiang, Yang; Ikeda, Jun-Ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-10-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  13. Histamine-induced increases in cyclic AMP levels in bovine adrenal medullary cells.

    OpenAIRE

    Marley, P. D.; Thomson, K. A.; Jachno, K.; Johnston, M. J.

    1991-01-01

    1. The effect of histamine on cellular cyclic AMP levels in cultured bovine adrenal medullary cells has been studied. 2. Histamine (0.3-30 microM) increased cyclic AMP levels transiently, with a maximal response after 5 min, a smaller response after 20 min, and no increase seen after 80 or 180 min. The EC50 at 5 min was approximately 2 microM. Histamine had no effect on cyclic AMP release from the cells over 5 min, but increased it after 90 min. 3. The cyclic AMP response to 5 microM histamin...

  14. A method for production and determination of histamine releasing activity from human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Kampen, G T; Poulsen, L K; Reimert, C M

    1997-01-01

    Histamine releasing factors, i.e. cytokines capable of inducing histamine release from basophils or mast cells, have been suggested to be involved in the pathogenesis of, for example, allergic late-phase reactions. Here we describe a controlled method for production and determination of histamine...... to an indirect effect on the basophils. Finally, neither the production of nor the response to HRA was dependent on the allergic status of the donor....

  15. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice Effect of Agarwood on Histamine Release and Scratching Behavior

    Directory of Open Access Journals (Sweden)

    Eiji Inoue

    2016-09-01

    Full Text Available Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A and compound 48/80-induced scratching behavior in mice were examined to investigate

  16. Exploring polyamine regulation by nascent histamine in a human-transfected cell model.

    Science.gov (United States)

    Abrighach, H; Fajardo, I; Sánchez-Jiménez, F; Urdiales, J L

    2010-02-01

    There are multiple lines of evidence suggesting interplay between histamine and polyamines in several mammalian cell types. However, the complex metabolic context makes it difficult to elucidate the mechanisms involved. Histamine's effects can be elicited after its binding to any of the four subtypes of G-protein coupled histamine membrane receptors. In addition, intracellular histamine can also interfere with polyamine metabolism, since there are several metabolic connections between the synthesis and degradation pathways of both types of amines. In order to dissect the metabolic effects of intracellular histamine on polyamine metabolism, we chose a well-known cell culture line, i.e., the human embryonic kidney 293 cells (HEK-293 cells). Initially, we show that HEK-293 cells lack a polyamine metabolic response to extracellular histamine, even over a wide range of histamine concentrations. HEK-293 cells were transfected with active and inactive versions of human histidine decarboxylase, and changes in many of the overlapping metabolic factors and limiting steps were tested. Overall, the results indicate a regulatory effect of histamine on the post-transcriptional expression of ornithine decarboxylase and suggest that this effect is primarily responsible for the decrease in polyamine synthesis and partial blockade of cell-cycle progression, which should affect cell proliferation rate.

  17. Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells

    DEFF Research Database (Denmark)

    Jensen, C; Svendsen, U G; Thastrup, Ole

    1987-01-01

    The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic...... acid moieties, was more potent than gangliosides with 2 moieties (GD1a and GD1b), which again were more potent inhibitors than GM1 with one moiety. Asialo-GM1 was without effect. In high concentrations the gangliosides potentiated basophil histamine release. The modulation of histamine release...

  18. Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells

    DEFF Research Database (Denmark)

    Jensen, C; Svendsen, U G; Thastrup, Ole

    1987-01-01

    acid moieties, was more potent than gangliosides with 2 moieties (GD1a and GD1b), which again were more potent inhibitors than GM1 with one moiety. Asialo-GM1 was without effect. In high concentrations the gangliosides potentiated basophil histamine release. The modulation of histamine release......The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic...

  19. Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Thastrup, Ole

    1987-01-01

    Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S...... with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane...... sialic acid in basophil leukocytes is involved in the regulation of histamine release, possibly by a modulation of the transmembraneous calcium fluxes preceding histamine release....

  20. Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

    DEFF Research Database (Denmark)

    Johansen, Torben

    1981-01-01

    The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior...... pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should...... be produced as the release of histamine takes place....

  1. Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells.

    Science.gov (United States)

    Stoyanov, Evgeniy; Uddin, Mohib; Mankuta, David; Dubinett, Steven M; Levi-Schaffer, Francesca

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an extremely low survival rate. It is characterized by a chronic inflammatory process with intense mast cell infiltrate that is associated with reduced survival. The aim of this study was to test the hypothesis that mast cells have an enhancing effect on NSCLC proliferation. To assess the tumor-promoting potential of mast cells, we used the human alveolar basal adenocarcinoma (A549) and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation rate of A549/LLC cells was markedly increased by mast cells and histamine. Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice treated with the mast cell stabilizer nedocromil sodium displayed an accelerated growth (number of metastic colonies in the lungs, total lung area and lung/total mice weight ratio). In summary, we have shown a significant effect of mast cells and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model in vivo we have found that mast cells are important negative regulators of cancer development. Therefore our results would indicate a pro-tumorogenic effect of the mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine targeted therapies should carefully consider this dual effect. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans.

    Science.gov (United States)

    Romero, Steven A; McCord, Jennifer L; Ely, Matthew R; Sieck, Dylan C; Buck, Tahisha M; Luttrell, Meredith J; MacLean, David A; Halliwill, John R

    2017-03-01

    In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H 1 and H 2 receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic knee-extension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either α-fluoromethylhistidine hydrochloride (α-FMH), a potent inhibitor of histidine decarboxylase, or histamine H 1 /H 2 -receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Δ) of 4.2 ± 1.8 ng/ml ( P histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise. NEW & NOTEWORTHY Blood flow to previously active skeletal muscle remains elevated following an acute bout of aerobic exercise and is dependent on activation of histamine H 1 and H 2 receptors. The intramuscular source of histamine that drives this response to exercise has not been identified. Using intramuscular microdialysis in exercising humans, we show both mast cell degranulation and formation of histamine by histidine decarboxylase contributes to the histamine-mediated vasodilation that occurs following a bout of aerobic exercise. Copyright © 2017 the American Physiological Society.

  3. Targeting of histamine producing cells by EGCG: a green dart against inflammation?

    Science.gov (United States)

    Melgarejo, Esther; Medina, Miguel Angel; Sánchez-Jiménez, Francisca; Urdiales, José Luis

    2010-09-01

    The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.

  4. Histamine as a Radiosensitizer of Malignant Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, E. S.; Medina, V.; Cricco, G.; Mohamed, N.; Croci, M.; Martin, G.; Nunez, M.; Bergoc, R. M.

    2004-07-01

    It has been established that the treatment with Histamine (Hi) produces a significant growth inhibition of different cell lines derived from human neoplasia. In a model of Knockout mice completely depleted of endogenous Hi, it was observed a significant delay in bone marroe repopulation after whole body irradiation. These results are in agreement with the hypothesis that histamine has a role in the regulation of haematopoiesis as well as an inhibitory effect on apoptosis. The objective of this paper was to study the possible effect of Hi as protector of normal cells and radiosensitizer of malignant ones. To study the effect of Hi on small-intestine and bone marrow, thirty made mice were randomly separeted into two groups: Control irradiated (C), and irradiated receiving Histamine (HI-group). All animals received a single dose of 10 Gy on whole-body employing a ''137Cs source of 189 TB{sub q} (Dose rate: 7.7 Gy/min) calibrated with TLD 700 dosimeter. Hi-group recieved a daily se injection (0.1 mg/kg) starting 20 hs before irradiation. Mice were sacrificed 5 days after irradiation. Histopathological analysis indicated that intestinal mucosae of C group showed important injury, whist mucosae of Hi-treated mice showed mild mucosal atrophy with conservation of villous projections and absence of vascular congestive changes. In order to investigate the effect of Hi on radiosensitivity of transformed cells, MDA-MB-231 (human breast carcinoma cells) were irradiated in vitro with doses ranging from 0 to 10 Gy. Results of radiobiological parameters indicate a significant increase on radiosensitivity of malignant cells. Employing specific fluorescent dyes and flow cytometric analysis we determined that the intracellular levels of hydrogen peroxide (H{sub 2}O{sub 2}) are significant increased by Hi 10 {mu}M in control and also in irradiated MDA-MB-231 cells, while the levels of superoxide (SO{sub 2}) were not significantly modified by Hi-treatment. (Author) 9 refs.

  5. Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes

    DEFF Research Database (Denmark)

    Clementsen, P; Milman, N; Struve-Christensen, E

    1991-01-01

    . No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A......23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria...

  6. Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

    OpenAIRE

    Rubinstein, I; Nadel, J A; Graf, P D; Caughey, G H

    1990-01-01

    Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes m...

  7. Homologous desensitization of human histamine H₃ receptors expressed in CHO-K1 cells.

    Science.gov (United States)

    Osorio-Espinoza, Angélica; Escamilla-Sánchez, Juan; Aquino-Jarquin, Guillermo; Arias-Montaño, José-Antonio

    2014-02-01

    Histamine H₃ receptors (H₃Rs) modulate the function of the nervous system at the pre- and post-synaptic levels. In this work we aimed to determine whether, as other G protein-coupled receptors (GPCRs), H₃Rs desensitize in response to agonist exposure. By using CHO-K1 cells stably transfected with the human H₃R (hH3R) we show that functional responses (inhibition of forskolin-induced cAMP accumulation in intact cells and stimulation of [(35)S]-GTPγS binding to cell membranes) were markedly reduced after agonist exposure. For cAMP accumulation assays the effect was significant at 60 min with a maximum at 90 min. Agonist exposure resulted in decreased binding sites for the radioligand [(3)H]-N-methyl-histamine ([(3)H]-NMHA) to intact cells and modified the sub-cellular distribution of H₃Rs, as detected by sucrose density gradients and [(3)H]-NMHA binding to cell membranes, suggesting receptor internalization. The reduction in the inhibition of forskolin-stimulated cAMP formation observed after agonist pre-incubation was prevented by incubation in hypertonic medium or in ice-cold medium. Agonist-induced loss in binding sites was also prevented by hypertonic medium or incubation at 4 °C, but not by filipin III, indicating clathrin-dependent endocytosis. Immunodetection showed that CHO-K1 cells express GPCR kinases (GRKs) 2/3, and both the GRK general inhibitor ZnCl₂ and a small interfering RNA against GRK-2 reduced receptor desensitization. Taken together these results indicate that hH₃Rs experience homologous desensitization upon prolonged exposure to agonists, and that this process involves the action of GRK-2 and internalization via clathrin-coated vesicles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Histamine inhibits adrenocortical cell proliferation but does not affect steroidogenesis.

    Science.gov (United States)

    Pagotto, Romina Maria; Pereyra, Elba Nora; Monzón, Casandra; Mondillo, Carolina; Pignataro, Omar Pedro

    2014-04-01

    Histamine (HA) is a neurotransmitter synthesized in most mammalian tissues exclusively by histidine decarboxylase enzyme. Among the plethora of actions mediated by HA, the modulatory effects on steroidogenesis and proliferation in Leydig cells (LCs) have been described recently. To determine whether the effects on LCs reported could be extrapolated to all steroidogenic systems, in this study, we assessed the effect of this amine on adrenal proliferation and steroidogenesis, using two adrenocortical cell lines as experimental models, murine Y1 cells and human NCI-H295R cells. Even when steroidogenesis was not modified by HA in adrenocortical cells, the biogenic amine inhibited the proliferation of H295R cells. This action was mediated by the activation of HRH1 subtype and an increase in the production of inositol phosphates as second messengers, causing cell-cycle arrest in the G2/M phase. These results indicate a new role for HA in the proliferation of human adrenocortical cells that could contribute to a better understanding of tumor pathology as well as to the development of new therapeutic agents.

  9. Histamine-stimulated expression of insulin-like growth factors in human glioma cells.

    OpenAIRE

    Van der Ven, L. T.; Van Buul-Offers, S. C.; Gloudemans, T.; Roholl, P. J.; Sussenbach, J. S.; Den Otter, W.

    1997-01-01

    Glioma tumour growth is associated with the expression of insulin-like growth factors I and II (IGFs) and of both type I and type II IGF receptors. It has also been shown that IGFs can stimulate proliferation of cultured glioma cells. We previously reported that histamine too can stimulate the growth of glioma cells in vitro. In this report, we study whether the histamine-induced growth of G47 glioma cells is mediated by the IGFs. We found that histamine stimulates the expression of both IGF-...

  10. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice: Effect of Agarwood on Histamine Release and Scratching Behavior.

    Science.gov (United States)

    Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Tsubonoya, Tomoe; Hayakawa, Tomomi; Sudoh, Keiichi

    2016-09-01

    This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

  11. Energy metabolism in rat mast cells in relation to histamine secretion

    DEFF Research Database (Denmark)

    Johansen, T

    1987-01-01

    of histamine was induced by the antigen-antibody reaction, the polymeric amine compound 48/80, and the divalent ionophore A23187. 2. In presence of low concentrations of metabolic inhibitors (oligomycin or antimycin A) a linear relation between the secretion of histamine induced by all three liberators...... and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast...... cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48...

  12. Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature

    DEFF Research Database (Denmark)

    Johansen, Torben

    1978-01-01

    1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature. 2 Histamine release induced by A23187 in the presence of calcium 10...

  13. Histamine downregulates the Th1-associated chemokine IP-10 in monocytes and myeloid dendritic cells.

    Science.gov (United States)

    Glatzer, Franziska; Mommert, Susanne; Köther, Brigitta; Gschwandtner, Maria; Stark, Holger; Werfel, Thomas; Gutzmer, Ralf

    2014-01-01

    Histamine is an important mediator of allergic diseases. It modulates the cytokine expression of various subtypes of antigen-presenting cells by four known receptors, H1R-H4R. The effects of histamine on myeloid dendritic cells (mDC) are unclear. Monocytes and mDC were isolated from human PBMC. Histamine receptor expression was evaluated by real-time PCR. Cells were stimulated with histamine and histamine receptor ligands, and restimulated with polyinosinic-polycytidylic acid (poly I:C), and supernatants were analyzed by protein array and ELISA. Monocytes and mDC express H1R and H2R without significant differences between the two cell types, whereas H4R mRNA was significantly higher in mDC compared with monocytes and H3R mRNA was not detected in any cell type. Prestimulation with histamine caused a significant decrease in poly I:C-induced expression of interferon-γ-induced protein (IP-10) in mDC and monocytes. Stimulation with specific H1R, H2R and H4R agonists and antagonists showed that the observed effect was mediated via H2R and H4R in monocytes and mDC. Monocytes and mDC have similar histamine receptor repertoires with regard to H1R, H2R and H3R, but H4R expression is higher on mDC. Histamine stimulation shows similar functional effects on both cell types, i.e., downregulation of TLR3-induced IP-10 production. This might be a new mechanism how histamine fosters a Th2 milieu. © 2013 S. Karger AG, Basel.

  14. Histamine immunocytochemistry

    DEFF Research Database (Denmark)

    Jacobi, H H; Johansson, O; Liang, Y

    2000-01-01

    We report that basophils in peripheral blood can be stained using histamine immunocytochemistry. The staining is based on the fixation of leucocytes with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (CDI) and the subsequent incubation of these cells with antisera raised against histamine...... conjugated to different carrier proteins using CDI. The staining appears to be specific for basophils and stained cells can be examined using both fluorescence microscopy and flow cytometry. In addition, histamine immunocytochemistry can be combined with conventional immunocytochemistry by incubating...... leucocytes with antibodies to cell surface antigens prior to or following fixation of the cells with CDI. Thus, histamine immunocytochemistry may be a valuable tool in future studies of human basophils....

  15. Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa

    Science.gov (United States)

    Xu, Xiang; Zhang, Hong; Song, Yuanlin; Lynch, Susan V.; Lowell, Clifford A.; Wiener-Kronish, Jeanine P.; Caughey, George H.

    2012-01-01

    Airway diseases often feature persistent neutrophilic inflammation and infection. In cystic fibrosis bronchitis, for example, Pseudomonas aeruginosa is isolated frequently. Previously, this laboratory revealed that neutrophils become major sources of histamine in mice with tracheobronchitis caused by the wall-less bacterium Mycoplasma pulmonis. To test the hypothesis that more-broadly pathogenic P. aeruginosa (which expresses cell wall-associated LPS and novel toxins) has similar effects, we incubated naïve mouse neutrophils with two strains of P. aeruginosa. Strain PAO1 greatly increased neutrophil histamine content and secretion, whereas strain PA103 depressed histamine production by killing neutrophils. The histamine-stimulating capacity of PAO1, but not PA103-mediated toxicity, persisted in heat-killed organisms. In PAO1-infected mice, lung and neutrophil histamine content increased. However, PAO1 did not alter production by mast cells (classical histamine reservoirs), which also resisted PA103 toxicity. To explore mechanisms of neutrophil-selective induction, we measured changes in mRNA encoding histidine decarboxylase (rate-limiting for histamine synthesis), probed involvement of endotoxin-TLR pathways in Myd88-deficient neutrophils, and examined contributions of pyocyanin and exotoxins. Results revealed that PAO1 increased histamine production by up-regulating histidine decarboxylase mRNA via pathways largely independent of TLR, pyocyanin, and type III secretion system exotoxins. PAO1 also increased histidine decarboxylase mRNA in neutrophils purified from infected lung. Stimulation required direct contact with neutrophils and was blocked by phagocytosis inhibitor cytochalasin D. In summary, Pseudomonas-augmented histamine production by neutrophils is strain-dependent in vitro and likely mediated by up-regulation of histidine decarboxylase. These findings raise the possibility that Pseudomonas-stimulated neutrophils can enhance airway inflammation by

  16. Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion

    DEFF Research Database (Denmark)

    Nielsen, E H; Johansen, Torben

    1986-01-01

    Nocodazole depolymerized microtubules and increased the number of microfilaments, and dimethylsulfoxide increased the number of microfilaments. Both drugs inhibited compound 48/80-induced histamine release from rat mast cells. Taxol, which increased the number of microtubules, had no effect...... on histamine release. These observations support the view that microtubules may not be directly involved in secretion, but apparently an increased number of microfilaments is associated with a decreased capacity of the mast cells for histamine release. We suggest that microfilaments have to be depolymerized...

  17. Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes

    DEFF Research Database (Denmark)

    Clementsen, P; Milman, N; Struve-Christensen, E

    1991-01-01

    Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. N......23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria...

  18. NK cell-mediated killing of AML blasts. Role of histamine, monocytes and reactive oxygen metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Brune, M.; Mellqvist, U.H. [Sahlgren`s Univ. Hospital, Dept. of Medicine, Haematology Section, Goeteborg (Sweden); Hansson, M.; Hermodsson, S.; Hellstrand, K. [Sahlgren`s Univ. Hospital, Dept. of Virology, Goeteborg (Sweden)

    1996-10-01

    Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologeous natural killer (NK) cells treated with NK cell-activating cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 {mu}M, abrogated the monocyte-induced inhibition of NK cells; thereby, histamine and IL-2 or histamine and IFN-{alpha} synergistically induced NK cell-mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts. (au) 19 refs.

  19. Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis.

    Science.gov (United States)

    Tamaka, Kyoko; Seike, Masahiro; Hagiwara, Tamio; Sato, Atsushi; Ohtsu, Hiroshi

    2015-04-01

    Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The effect of tartrazine on histamine release from rat peritoneal mast cells.

    Science.gov (United States)

    Safford, R J; Goodwin, B F

    1984-01-01

    The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10(-5) to 10(-2)M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10(-3) and 10(-4)M. Augmentation of ionophore induced release was maximal at between 0-5 min preincubation of the cells with tartrazine.

  1. Quantitative electrophysiological monitoring of anti-histamine drug effects on live cells via reusable sensor platforms.

    Science.gov (United States)

    Pham Ba, Viet Anh; Cho, Dong-Guk; Kim, Daesan; Yoo, Haneul; Ta, Van-Thao; Hong, Seunghun

    2017-08-15

    We demonstrated the quantitative electrophysiological monitoring of histamine and anti-histamine drug effects on live cells via reusable sensor platforms based on carbon nanotube transistors. This method enabled us to monitor the real-time electrophysiological responses of a single HeLa cell to histamine with different concentrations. The measured electrophysiological responses were attributed to the activity of histamine type 1 receptors on a HeLa cell membrane by histamine. Furthermore, the effects of anti-histamine drugs such as cetirizine or chlorphenamine on the electrophysiological activities of HeLa cells were also evaluated quantitatively. Significantly, we utilized only a single device to monitor the responses of multiple HeLa cells to each drug, which allowed us to quantitatively analyze the antihistamine drug effects on live cells without errors from the device-to-device variation in device characteristics. Such quantitative evaluation capability of our method would promise versatile applications such as drug screening and nanoscale bio sensor researches. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effect of histamine on Ca(2+)-dependent signaling pathways in rat conjunctival goblet cells.

    Science.gov (United States)

    Li, Dayu; Carozza, Richard B; Shatos, Marie A; Hodges, Robin R; Dartt, Darlene A

    2012-10-05

    The purpose of this study was to determine the Ca(2+)-dependent cellular signaling pathways used by histamine to stimulate conjunctival goblet cell secretion. Cultured rat goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured by loading cultured cells with the Ca(2+) sensitive dye fura-2. The level of [Ca(2+)](i) was measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2 was depleted using small interfering RNA (siRNA). Histamine-stimulated conjunctival goblet cell secretion of high molecular weight glycoproteins was blocked by removal of extracellular Ca(2+) and depletion of ERK2 by siRNA. Histamine increase in [Ca(2+)](i) was desensitized by repeated addition of agonist and blocked by a phospholipase C antagonist. Histamine at higher doses increased [Ca(2+)](i) by stimulating influx of extracellular Ca(2+), but at a lower dose released Ca(2+) from intracellular stores. Activation of each histamine receptor subtype (H(1)-H(4)) increased [Ca(2+)](i) and histamine stimulation was blocked by antagonists of each receptor subtype. The H(2) receptor subtype increase in [Ca(2+)](i) was cAMP dependent. We conclude that histamine activates phospholipase C to release intracellular Ca(2+) that induces the influx of extracellular Ca(2+) and activates ERK1/2 to stimulate conjunctival goblet cell mucous secretion, and that activation of all four histamine receptor subtypes can increase [Ca(2+)](i).

  3. Co-Effect of Histamine on Ca2+-Dependent Signaling Pathways in Rat Conjunctival Goblet Cells

    Science.gov (United States)

    Li, Dayu; Carozza, Richard B.; Shatos, Marie A.; Hodges, Robin R.; Dartt, Darlene A.

    2012-01-01

    Purpose. The purpose of this study was to determine the Ca2+-dependent cellular signaling pathways used by histamine to stimulate conjunctival goblet cell secretion. Methods. Cultured rat goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay. Intracellular [Ca2+] ([Ca2+]i) was measured by loading cultured cells with the Ca2+ sensitive dye fura-2. The level of [Ca2+]i was measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2 was depleted using small interfering RNA (siRNA). Results. Histamine-stimulated conjunctival goblet cell secretion of high molecular weight glycoproteins was blocked by removal of extracellular Ca2+ and depletion of ERK2 by siRNA. Histamine increase in [Ca2+]i was desensitized by repeated addition of agonist and blocked by a phospholipase C antagonist. Histamine at higher doses increased [Ca2+]i by stimulating influx of extracellular Ca2+, but at a lower dose released Ca2+ from intracellular stores. Activation of each histamine receptor subtype (H1–H4) increased [Ca2+]i and histamine stimulation was blocked by antagonists of each receptor subtype. The H2 receptor subtype increase in [Ca2+]i was cAMP dependent. Conclusions. We conclude that histamine activates phospholipase C to release intracellular Ca2+ that induces the influx of extracellular Ca2+ and activates ERK1/2 to stimulate conjunctival goblet cell mucous secretion, and that activation of all four histamine receptor subtypes can increase [Ca2+]i. PMID:22956601

  4. Synergistic effect of histamine and TNF-α on monocyte adhesion to vascular endothelial cells.

    Science.gov (United States)

    Chen, Chong; Khismatullin, Damir B

    2013-04-01

    The histamine level is high during allergic attacks, and patients with allergy may have chronic inflammatory conditions at which tumor necrosis factor (TNF)-α is extensively released by macrophages. Here, in vitro static and microfluidic flow assays were conducted to investigate the combined influence of histamine and TNF-α on adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVEC). In a static assay, histamine stimulation of TNF-α-activated HUVEC elevated the number of attached THP-1 cells. In a flow assay, the number of crawling and firmly adherent THP-1 cells was higher on TNF-α + histamine activated HUVEC than on HUVEC activated by TNF-α alone. This synergistic effect of histamine and TNF-α is caused by the increased endothelial surface expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Since the exposure of TNF-α-activated endothelium to histamine favors monocyte recruitment, it may be a serious risk factor for atherosclerosis and other inflammatory disorders.

  5. Effect of ouabain, digoxin and digitoxigenin on potassium uptake and histamine release from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Knudsen, T; Ferjan, I; Johansen, Torben

    1993-01-01

    Rat peritoneal mast cells were used to study the effects of digitalis glycosides on potassium uptake and histamine release induced by compound 48/80, substance P and egg-albumin (immunological release). In the absence of calcium all glycosides inhibited potassium uptake. Ouabain and digoxin...... enhanced the histamine release while digitoxigenin either had no effect or was slightly inhibitory. In the presence of calcium, the glycosides only affected potassium uptake and histamine release slightly. In the presence of lithium or lanthanum the enhancement of the histamine release was counteracted....... Hydrophilic digitalis glycosides seem to enhance histamine release secondary to an increase in intracellular sodium. Lipophilic glycosides have no effect on the release....

  6. Effects of histamine on ciliary beat frequency of ciliated cells from guinea pigs nasal mucosa.

    Science.gov (United States)

    An, Fengwei; Xing, Lijun; Zhang, Zhiqiang; Chen, Lei

    2015-10-01

    We aimed to investigate the effect of histamine on ciliary beat frequency (CBF) through combining high-speed digital microscopy and patch-clamp technology. Ciliated cells were obtained from septum and turbinate of 90-120-day-old healthy male guinea pigs. Tight seal was formed by applying negative pressure on the glass electrode after the drawing and pushing progress. Then, we enrolled high-speed digital microscopy to measure CBF before and after treatment with histamine of different concentrations ranging from 10(-6) to 10(-1) mol/L in Hank's solution and D-Hank's solution as well as after administrating adenosine triphosphate. One-way ANOVA, Student's t test or Kruskal-Wallis test was used for statistical comparisons. Glass electrode fix up ciliated cell is available at tip diameter of 2-5 μm and negative pressure of 10-20 cmH2O column. The baseline CBF in Hank's solution was higher than in D-Hank's solution. Treatment with 10(-6)-l0(-3) mol/L histamine of concentrations can stimulate a rise of CBF. Nevertheless, CBF in all groups decreased to baseline CBF within 20 min. Generally, 10(-2) mol/L histamine can stimulate a rise of CBF; meanwhile, the high concentration of histamine killed 50% ciliated cell. Histamine at 10(-1) mol/L killed all ciliated cells. Ciliary beating activity decreased in Ca(2+)-free solution. Moreover, adenosine triphosphate could increase CBF effectively after the stimulation effect of histamine. We construct an effective technology integrating patch-clamp technique with CBF measurements on ciliated cells. Extracellular histamine stimulation could increase CBF effectively.

  7. Histamine receptors of cones and horizontal cells in Old World monkey retinas.

    Science.gov (United States)

    Vila, Alejandro; Satoh, Hiromasa; Rangel, Carolina; Mills, Stephen L; Hoshi, Hideo; O'Brien, John; Marshak, Daniel R; Macleish, Peter R; Marshak, David W

    2012-02-15

    In primates the retina receives input from histaminergic neurons in the posterior hypothalamus that are active during the day. In order to understand how this input contributes to information processing in Old World monkey retinas, we have been localizing histamine receptors (HR) and studying the effects of histamine on the neurons that express them. Previously, we localized HR3 to the tips of ON bipolar cell dendrites and showed that histamine hyperpolarizes the cells via this receptor. We raised antisera against synthetic peptides corresponding to an extracellular domain of HR1 between the 4th and 5th transmembrane domains and to an intracellular domain near the carboxyl terminus of HR2. Using these, we localized HR1 to horizontal cells and a small number of amacrine cells and localized HR2 to puncta closely associated with synaptic ribbons inside cone pedicles. Consistent with this, HR1 mRNA was detected in horizontal cell perikarya and primary dendrites and HR2 mRNA was found in cone inner segments. We studied the effect of 5 μM exogenous histamine on primate cones in macaque retinal slices. Histamine reduced I(h) at moderately hyperpolarized potentials, but not the maximal current. This would be expected to increase the operating range of cones and conserve ATP in bright, ambient light. Thus, all three major targets of histamine are in the outer plexiform layer, but the retinopetal axons containing histamine terminate in the inner plexiform layer. Taken together, the findings in these three studies suggest that histamine acts primarily via volume transmission in primate retina. Copyright © 2011 Wiley-Liss, Inc.

  8. The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture.

    Science.gov (United States)

    Del Rio, Beatriz; Redruello, Begoña; Linares, Daniel M; Ladero, Victor; Fernandez, Maria; Martin, Maria Cruz; Ruas-Madiedo, Patricia; Alvarez, Miguel A

    2017-03-01

    Tyramine and histamine are the biogenic amines (BA) most commonly found at high concentrations in food; they may even appear together at toxic concentrations. The present work examines, via real-time cell analysis, whether histamine and tyramine show synergistic toxicity towards intestinal cell cultures. Employing a constant equipotency ratio, their interaction was examined via the combination index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was associated with a stronger cytotoxic effect than was treatment with either BA or on its own. Indeed, a synergistic interaction (CIhistamine, at concentrations below the legal limit, increases the cytotoxicity of tyramine at concentrations frequently reached in some foods. The synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits designed to ensure consumer safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries.

    Science.gov (United States)

    Dalgaard, E G; Andersen, K; Svenningsen, P; Hansen, P B L

    2017-01-01

    The aims were to develop a method for real-time detection of histamine release and to test whether incubation with aldosterone induces histamine release from isolated, perfused mice mesenteric arteries. Fura-2-loaded HEK-293 cells transfected with the histamine H1 receptor was used as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca 2+ transient peaks using fluorescence imaging. The developed biosensor was sensitive to histamine in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild-type mice for 50 min resulted in an increased number of intracellular Ca 2+ transient peaks in the biosensor cells, which was significantly inhibited by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell-deficient SASH mice induced similar pyrilamine-sensitive Ca 2+ transient response in the biosensor cells. Mesenteric arteries from wild-type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only source of histamine release. The developed biosensor assay can measure release of substances from vascular preparations. Histamine is released from the vessel preparation in response to aldosterone treatment independently of mast cells. The assay enables us to study a new signaling mechanism for vascular responses induced by aldosterone. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Characterization and function of histamine receptors in human bone marrow stromal cells.

    Science.gov (United States)

    Nemeth, Krisztian; Wilson, Todd; Rada, Balazs; Parmelee, Alissa; Mayer, Balazs; Buzas, Edit; Falus, Andras; Key, Sharon; Masszi, Tamas; Karpati, Sarolta; Mezey, Eva

    2012-02-01

    There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL-6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs. Copyright © 2011 AlphaMed Press.

  11. Radiation-released histamine in the rhesus monkey as modified by mast cell depletion and antihistamine. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, T.F.; Strike, T.A.

    1975-06-01

    Changes in blood histamine concentrations of rhesus monkeys were measured after a 4000-rad dose of mixed gamma-neutron radiation. All animals were pretreated with amino-guanidine to retard histamine catabolism. Histamine concentrations increased from 26 + or - 13.5 to 235 + or - 16 ng/ml after irradiation. When the animals were pretreated with an antihistamine, chlorpheniramine (3 mg/kg), histamine concentrations changed from 25.7 + or - 13.5 to 462 + or - 226 ng/ml after irradiation. When the monkeys were pretreated with a specific mast cell histamine depleter, compound 48/80 (1mg/kg per day) for four consecutive days and then irradiated (4000 rads), histamine concentrations did not change significantly. When 48/80 was given 20 min after irradiation, histamine concentrations changed from 18 + or - 2 ng/ml to a maximum of 35 + or - 9 ng/ml after 48/80 injection. (Author) (GRA)

  12. Effects of H[sub 1]-receptor antagonists on [sup 14]C-aminopyrine accumulated in histamine-stimulated rabbit gastric glands

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, G.; Romell, B.; Girma, K.; Seensalu, R. (Swedish Univ. of Agricultural Science, Uppsala (Sweden))

    1993-01-01

    After stimulation of gastric acid production there is a considerable delay before the acid starts to appear in the gastric lumen. The present study was carried out on isolated gastric glands to test the hypothesis that there may be a mechanisms in the parietal cell that contributes to this delay by preventing emptying of the secretory canaliculi. Glands were incubated with [sup 14]C-aminopyrine and stimulated with histamine. After accumulation of [sup 14]C-aminopyrine, various concentration of H[sub 1]-receptor antagonists were added. Clemastine, promethazine, and hydroxyzine effectively and cetirizine and tripelennamine less effectively decreased the accumulated [sup 14]C-aminopyrine content in a dose-dependent manner without significantly reducing the oxygen consumption. The H[sub 1]-receptor antagonists influenced the [sup 14]C-aminopyrine content in another manner than H[sub 2]-receptor antagonists. No effects were obtained by atropine or lidocaine, indicating that the elimination of [sup 14]C-amionopyrine is not an inticholinergic effect or due to membrane effects as exerted by local anesthetics. Stimulation of glands by further addition of histamine did not significantly stimulate the uptake of [sup 14]C-aminopyrine in the glands, whereas stimulation with db-cAMP produced an increase that was most pronounced when low concentrations of hydroxyzine had been used. It is suggested that H[sub 1]-receptor antagonists do not inhibit stimulation of acid production in the secretory canaliculi. They may, however, interfere with a mechanism preventing acid from leaving the parietal cell. Such a mechanism may contribute to the delay in appearance of acid in the gastric lumen after stimulation of gastric acid production. 37 refs., 7 figs.

  13. The anti-anaphylactic and histamine-releasing properties of the antihistamines. Their effect on the mast cells

    Science.gov (United States)

    Mota, I.; Da Silva, W. Dias

    1960-01-01

    It has been shown that, depending upon their concentration, antihistamines act in three different ways: (a) by competitive inhibition of histamine as already known; (b) by destroying mast cells and releasing histamine; and (c) by preventing mast cell damage and histamine release in anaphylaxis. Furthermore, antihistamines potentiated mast cell damage and histamine release by compound 48/80, when acting on guinea-pig tissues, and inhibited these same phenomena when acting on rat tissues. It is concluded that the effect of antihistamines in anaphylaxis is possibly due both to their competitive inhibition of histamine on smooth muscle receptors and to their inhibition of mast cell damage and histamine release by antigen. PMID:13773171

  14. Bradykinin and histamine-induced cytosolic calcium increase in capillary endothelial cells of bovine adrenal medulla.

    Science.gov (United States)

    Vinet, Raúl; Cortés, Magdalena P; Alvarez, Rocío; Delpiano, Marco A

    2014-09-01

    We have assessed the effect of bradykinin and histamine on the cytosolic free calcium concentration ([Ca(2+)]i ) of bovine adrenal medulla capillary endothelial cells (BAMCECs). To measure [Ca(2+)]i changes in BAMCECs the intracellular fluorescent probe, fluo-3 AM, was used. Bradykinin (3 µM) produced a transient monophasic increase in [Ca(2+)]i , which was depressed by B1650 (0.1 µM), a B2-bradykinin receptor antagonist (D-Arg-[Hyp(3), Thi(5,8) , D-Phe(7)]-Bradykinin). Similarly, increase in [Ca(2+)]i induced by histamine was also depressed by tripolidine (0.1 µM), an H1-histamine receptor antagonist. [Ca(2+)]i increase induced by both agonists was unaffected in the absence of extracellular Ca(2+) or presence of antagonists of voltage operated Ca(2+) channels (VOCCs). Thapsigargin (1 µM) did not abolish the increase of [Ca(2+)]i produced by bradykinin, but abolished that of histamine. In contrast, caffeine (100 µM), abolished the [Ca(2+)]i response induced by bradykinin (3 µM), but did not affect the [Ca(2+)]i increase induced by histamine (100 µM). The results indicate the presence of B2 bradykinin- and H1 histamine-receptors in BAMCECs. Liberation of Ca(2+) induced by both agonists occurs through 2 different intracellular mechanisms. While bradykinin activates a sarco(endo) plasmic reticulum (SER) containing a SER Ca(2+) -ATPase (SERCA) thapsigargin-insensitive, histamine activates a SER containing a SERCA thapsigargin-sensitive. We suggest that the increase in [Ca(2+)]i induced by bradykinin and histamine could be of physiological relevance, modulating adrenal gland microcirculation. © 2014 International Federation for Cell Biology.

  15. Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice.

    Science.gov (United States)

    Kinbara, Masayuki; Bando, Kanan; Shiraishi, Daisuke; Kuroishi, Toshinobu; Nagai, Yasuhiro; Ohtsu, Hiroshi; Takano-Yamamoto, Teruko; Sugawara, Shunji; Endo, Yasuo

    2016-06-01

    We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase (HDC-KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2 -lipopolysaccharide (LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2 . Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 mm or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni-TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni-TI. Pyrilamine and cromoglicate reduced either the Ni-TI or the ensuing allergic inflammation when administered before Ni-TI (at either the sensitization or elicitation step), but not if administered when the Ni-TI had subsided. Experiments on HDC-KO and H1-receptor-KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni-TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni-TI by drugs may be effective at preventing or reducing Ni allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Histamine prevents radiation-induced mesenchymal changes in breast cancer cells.

    Science.gov (United States)

    Galarza, Tamara E; Mohamad, Nora A; Táquez Delgado, Mónica A; Vedoya, Guadalupe M; Crescenti, Ernesto J; Bergoc, Rosa M; Martín, Gabriela A; Cricco, Graciela P

    2016-09-01

    Radiotherapy is a prime option for treatment of solid tumors including breast cancer though side effects are usually present. Experimental evidence shows an increase in invasiveness of several neoplastic cell types through conventional tumor irradiation. The induction of epithelial to mesenchymal transition is proposed as an underlying cause of metastasis triggered by gamma irradiation. Experiments were conducted to investigate the role of histamine on the ionizing radiation-induced epithelial to mesenchymal transition events in breast cancer cells with different invasive phenotype. We also evaluated the potential involvement of Src phosphorylation in the migratory capability of irradiated cells upon histamine treatment. MCF-7 and MDA-MB-231 mammary tumor cells were exposed to a single dose of 2Gy of gamma radiation and five days after irradiation mesenchymal-like phenotypic changes were observed by optical microscope. The expression and subcellular localization of E-cadherin, β-catenin, vimentin and Slug were determined by immunoblot and indirect immunofluorescence. There was a decrease in the epithelial marker E-cadherin expression and an increase in the mesenchymal marker vimentin after irradiation. E-cadherin and β-catenin were mainly localized in cytoplasm. Slug positive nuclei, matrix metalloproteinase-2 activity and cell migration and invasion were significantly increased. In addition, a significant enhancement in Src phosphorylation/activation could be determined by immunoblot in irradiated cells. MCF-7 and MDA-MB-231 cells also received 1 or 20μM histamine during 24h previous to be irradiated. Notably, pre-treatment of breast cancer cells with 20μM histamine prevented the mesenchymal changes induced by ionizing radiation and also reduced the migratory behavior of irradiated cells decreasing phospho-Src levels. Collectively, our results suggest that histamine may block events related to epithelial to mesenchymal transition in irradiated mammary cancer

  17. Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells.

    Science.gov (United States)

    Martin, Rebecca K; Saleem, Sheinei J; Folgosa, Lauren; Zellner, Hannah B; Damle, Sheela R; Nguyen, Giang-Kim T; Ryan, John J; Bear, Harry D; Irani, Anne-Marie; Conrad, Daniel H

    2014-07-01

    It has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate that the lack of MCs also influences MDSC trafficking. Preferential trafficking to the liver was not seen in MC-deficient mice. In addition, evidence that the MC mediator histamine was important in MDSC trafficking and activation is also shown. MDSCs express HR1-3. Blockade of these receptors by HR1 or HR2 antagonists reversed the histamine enhancement of MDSC survival and proliferation observed in cell culture. In addition, histamine differentially influenced Arg1 and iNOS gene expression in MDSCs and greatly enhanced IL-4 and IL-13 message, especially in granulocytic MDSCs. Evidence that histamine influenced activity seen in vitro translated to in vivo when HR1 and HR2 antagonists blocked the effect of MDSCs on parasite expulsion and tumor metastasis. All of these data support the MDSC-mediated promotion of Th2 immunity, leading to the suggestion that allergic-prone individuals would have elevated MDSC levels. This was directly demonstrated by looking at the relative MDSC levels in allergic versus control patients. Monocytic MDSCs trended higher, whereas granulocytic MDSCs were increased significantly in allergic patients. Taken together, our studies indicate that MCs and MC-released histamine are critical for MDSC-mediated immune regulation, and this interaction should be taken into consideration for therapeutic interventions that target MDSCs. © 2014 Society for Leukocyte Biology.

  18. Mast cells down-regulate CD4+CD25+ T regulatory cell suppressor function via histamine H1 receptor interaction.

    Science.gov (United States)

    Forward, Nicholas A; Furlong, Suzanne J; Yang, Yongjun; Lin, Tong-Jun; Hoskin, David W

    2009-09-01

    Mast cells promote both innate and acquired immune responses, but little is known about the effect of mast cells on T regulatory (T(reg)) cell function. In this study, we show for the first time that the capacity of murine CD4(+)CD25(+) T(reg) cells to suppress in vitro proliferation by CD4(+)CD25(-) T responder (T(resp)) cells in response to anti-CD3/anti-CD28 mAb-coated beads was reduced in the presence of syngeneic bone marrow-derived mast cells (BMMC) activated by FcepsilonR cross-linking. Activated BMMC culture supernatants or exogenous histamine also inhibited T(reg) cell suppressor function while the histamine H1 receptor-specific antagonist loratadine, but not the H2 receptor-specific antagonist famotidine, restored T(reg) cell suppressor function in the presence of activated BMMC or activated BMMC culture supernatants. Moreover, treatment of T(reg) cells with loratadine, but not famotidine, rescued T(reg) cell suppressor function in the presence of exogenous histamine. In addition, the H1 receptor-specific agonist 2-pyridylethylamine dihydrochloride inhibited T(reg) cell suppressor function to an extent that was comparable to histamine, whereas the H2 receptor-specific agonist amthamine dihydrobromide was without effect. Both T(reg) cells and T(resp) cells expressed H1 receptors. Exposure to histamine caused T(reg) cells to express lower levels of CD25 and the T(reg) cell-specific transcription factor Foxp3. Taken together, these data indicate that BMMC-elaborated histamine inhibited T(reg) cell suppressor function by signaling through the H1 receptor. We suggest that histamine released as a result of mast cell activation by microbial products might cause a transient decrease in T(reg) cell suppressor function, thereby enhancing the development of protective immunity.

  19. Estimation of adenosine triphosphate utilization of rat mast cells during and after anaphylactic histamine secretion

    DEFF Research Database (Denmark)

    Johansen, Torben

    1990-01-01

    Determination of the cellular content of adenosine triphosphate (ATP) and the rate of ATP-synthesis were used to estimate the cellular utilization of ATP in relation to anaphylactic histamine secretion. There was an increased rate of oxidative ATP-synthesis and a decreased cellular ATP content...... during the time period of histamine secretion and immediately after its completion. During secretion the additional ATP-utilization above the basal level of ATP-synthesis was 0.51 pmol/10(3) cells. 2.5 min after cell activation, the rate of additional ATP-utilization was 0.30 pmol/10(3) cells...

  20. Effect of oestradiol on mast cell number and histamine level in the mammary glands of rat.

    Science.gov (United States)

    Jing, H; Wang, Z; Chen, Y

    2012-06-01

    Variations of mast cell number, histamine concentration and oestrogen receptor (ER) expression in mammary glands with the fluctuation of plasma oestradiol level were identified either in the intact rats at different oestrous stages or in the ovary-ectomized rats administrated with different doses of oestradiol benzoate. The results showed that the number of mast cells and histamine concentration fluctuated concomitantly with plasma oestradiol level during the oestrous cycle. More mast cell number and higher histamine concentrations were observed in the oestrous stage than that in the prooestrous and dioestrous stages. Ovariectomy decreased the mast cell number and histamine concentration, which were reconstituted by exogenous oestradiol. ER was mainly found in the nuclear of epithelial cells and interstitial cells of mammary glands. In addition, ER was also expressed in the cytoplasm of some stromal cells. These stromal cells were verified to be mast cells. In conclusion, our results suggested that oestradiol modulated mast cell number and its degranulation in the mammary gland through the ERs pathway. © 2011 Blackwell Verlag GmbH.

  1. Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes

    DEFF Research Database (Denmark)

    Clementsen, P; Milman, N; Struve-Christensen, E

    1991-01-01

    Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. N......23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria......-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections....

  2. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

    Directory of Open Access Journals (Sweden)

    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  3. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

    Science.gov (United States)

    Kang, Ji-Ah; Lee, Keimin; Lee, Kwang Min; Cho, Sukhee; Seo, Jinsoo; Hur, Eun-Mi; Park, Chul-Seung; Baik, Ja-Hyun; Choi, Se-Young

    2012-01-01

    The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+) evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+) increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+) increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  4. Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Hu XF

    2015-08-01

    Full Text Available Xiufen Hu,1,* Mohammad Ishraq Zafar,2,* Feng Gao2 1Department of Paediatrics, Tongji Hospital, 2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs and the influence of lipopolysaccharide (LPS, histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colony-stimulating factor (GM-CSF alone or with interleukin (IL-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL. We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA323–339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-γ production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4- than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days

  5. Regulation of human skin mast cell histamine release by PDE inhibitors.

    Science.gov (United States)

    Eskandari, N; Bastan, R; Peachell, P T

    2015-01-01

    Mast cell and basophiles are thought to be central to inflammation that has an allergic basis as allergens activate these cells in an IgE-dependent manner to generate mediators such as histamine, eicosanoids and cytokines. Phosphodiesterase (PDE) is known to exist as multiple molecular forms of enzyme that metabolise the second messengers. Studies of our own have shown that, of a variety of isoform-selective drugs, the PDE4-selective inhibitors, such as rolipram, attenuate the IgE-mediated release of histamine from human basophiles but not from human lung mast cells (HLMC). The main aim of the present study was to characterise the type and role of PDEs regulating human skin mast cells by using selective and non-selective PDE inhibitors. Cells were pre-treated for 15 min with these agents and then challenged with an optimal releasing concentration of anti IgE (1:300) for a further 25 min for the release of histamine. The data show that all the selective PDE-inhibitor compounds (10(-5)M) were ineffective whereas the non-selective PDE inhibitor, theophylline (10(-3)M), inhibited histamine release from HSMC (74 ± 4% inhibition; peffect on histamine release from HLMC whereas, in basophiles, compounds with activity at PDE 4 (rolipram, denbufylline, Ro-2017, Org 30029) were effective inhibitors of histamine release. The data suggest that unlike most inflammatory cells, PDE-selective inhibitors are ineffective stabilisers of HSMC activity which is similar to HLMC. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  6. Effect of amiloride on arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A...

  7. Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects of inflammatory cells

    NARCIS (Netherlands)

    Beek, van L.M.; Mulder, M.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell

  8. Histamine regulates relevant murine dendritic cell functions via H4 receptor.

    Science.gov (United States)

    Simon, Tunde; Laszlo, Valeria; Lang, Orsolya; Buzas, Edit; Falus, Andras

    2011-06-01

    Histamine, produced by dendritic cells (DCs) or by other cells of the immune system, may have significant impact on DC activities. We investigated the influence of histamine and histamine H4 receptor (H4R) on some relevant functions of DCs. Histamine significantly decreased the antigen presentation capacity of splenic DCs, and this effect was reversed by a H4R antagonist. Furthermore, enhanced antigen presentation was detected in H4R-/- DCs. Prolonged histamine treatment during DC differentiation stimulated migration, albeit the increase was not significant. H4R-deficient DCs possessed significantly lower migration capacity than their wild-type counterparts. Monitoring in vivo and in vitro DC cytokine production revealed that a H4R agonist in combination with LPS, increased IL-1 beta mRNA expression, and a H4R antagonist reversed this effect. In H4R-deficient mice we detected decreased mRNA expression of some DC-derived cytokines including IFN-gamma and IL-10. Upon CFA stimulation, genotype-dependent differences were found in the expression of IL-6 and IFN-gamma. Our data suggest that H4R plays a crucial role in variety of functions of murine DCs.

  9. The inhibitory effect of simvastatin and aspirin on histamine responsiveness in human vascular endothelial cells.

    Science.gov (United States)

    Absi, Mais; Bruce, Jason I; Ward, Donald T

    2014-04-01

    Statins and aspirin deliver well-established cardiovascular benefits resulting in their increased use as combined polypills to decrease risk of stroke and heart disease. However, the direct endothelial effect of combined statin/aspirin cotreatment remains unclear. Histamine is an inflammatory mediator that increases vascular permeability, and so we examined the effect of treating human umbilical vein endothelial cells (HUVECs) for 24 h with 1 μM simvastatin and 100 μM aspirin on histamine responsiveness. Subsequent histamine (1 μM) challenge increased intracellular calcium (Ca(2+)i) concentration, an effect that was significantly inhibited by combined simvastatin/aspirin pretreatment but not when then the compounds were given separately, even at 10-fold higher concentrations. In contrast, the Ca(2+)i mobilization response to ATP challenge (10 μM) was not inhibited by combined simvastatin/aspirin pretreatment. The H1 receptor antagonist pyrilamine significantly inhibited both histamine-induced Ca(2+)i mobilization and extracellular signal-regulated kinase (ERK) activation, whereas ranitidine (H2 receptor antagonist) was without effect. However, combined simvastatin/aspirin pretreatment failed to decrease H1 receptor protein expression ruling out receptor downregulation as the mechanism of action. Histamine-induced ERK activation was also inhibited by atorvastatin pretreatment, while simvastatin further inhibited histamine-induced vascular endothelial cadherin phosphorylation as well as altered HUVEC morphology and inhibited actin polymerization. Therefore, in addition to the known therapeutic benefits of statins and aspirin, here we provide initial cellular evidence that combined statin/aspirin treatment inhibits histamine responsiveness in HUVECs.

  10. Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway.

    Science.gov (United States)

    Sun, Xudong; Yuan, Xue; Chen, Liang; Wang, Tingting; Wang, Zhe; Sun, Guoquan; Li, Xiaobing; Li, Xinwei; Liu, Guowen

    2017-01-01

    Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

  11. Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.

    Science.gov (United States)

    Purkiss, J. R.; West, D.; Wilkes, L. C.; Scott, C.; Yarrow, P.; Wilkinson, G. F.; Boarder, M. R.

    1994-01-01

    1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence. PMID:8032588

  12. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Directory of Open Access Journals (Sweden)

    Sachiko Chikahisa

    Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  13. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Science.gov (United States)

    Chikahisa, Sachiko; Kodama, Tohru; Soya, Atsushi; Sagawa, Yohei; Ishimaru, Yuji; Séi, Hiroyoshi; Nishino, Seiji

    2013-01-01

    Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v)) mice. No significant difference was found in the basal amount of sleep/wake between W/W(v) mice and their wild-type littermates (WT), although W/W(v) mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v) mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v) mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v) mice. W/W(v) mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  14. Modulation of astrocytic glutamine synthetase expression and cell viability by histamine in cultured cortical astrocytes exposed to OGD insults.

    Science.gov (United States)

    Wang, Xiao-Fen; Hu, Wei-Wei; Yan, Hai-Jing; Tan, Li; Gao, Jie-Qiong; Tian, Yue-Yang; Shi, Xiao-Jie; Hou, Wei-Wei; Li, Juan; Shen, Yao; Chen, Zhong

    2013-08-09

    Histamine, a neurotransmitter or neuromodulator has been demonstrated to be neuroprotective in cerebral ischemia. However, few reports concern its function on astrocytes during cerebral ischemia. The purpose of this study was to investigate the effects of histamine on astrocytic cell damage and glutamate signaling, especially on glutamine synthetase (GS) expression in primary cultured cortical astrocytes exposed to oxygen-glucose deprivation (OGD) insult. OGD for 6h caused a severe damage of astrocytic mitochondrial function, and decreased GS expression and then increased the extracellular glutamate level. Pretreatment with histamine significantly prevented the cell damage and rescued the expression of GS in a concentration-dependent manner. The protective effect of histamine on astrocytic cell damage could be partly reversed either by H1 receptor antagonist pyrilamine or H2 receptor antagonist cimetidine. However, the regulatory effect of histamine on GS expression was antagonized only by pyrilamine. In addition, bisindolylmaleimide II, a broad-spectrum inhibitor of PKC, reversed the regulatory action of histamine on GS expression. These results indicate that histamine can effectively protect against OGD-induced cell damage in astrocytes through H1 and H2 receptors, and its regulatory effect on astrocytic GS expression may be due to the activation of H1 receptor and PKC pathway. Histamine may be an endogenous protective factor and calls for its further study as a regulator of astrocyte function during ischemic stroke. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Lipopolysaccharide induces H1 receptor expression and enhances histamine responsiveness in human coronary artery endothelial cells.

    Science.gov (United States)

    Raveendran, Vineesh V; Tan, Xiaoyu; Sweeney, Matthew E; Levant, Beth; Slusser, Joyce; Stechschulte, Daniel J; Dileepan, Kottarappat N

    2011-04-01

    Summary Histamine is a well-recognized modulator of vascular inflammation. We have shown that histamine, acting via H1 receptors (H1R), synergizes lipopolysaccharide (LPS)-induced production of prostaglandin I(2) (PGI(2)), PGE(2) and interleukin-6 (IL-6) by endothelial cells. The synergy between histamine and LPS was partly attributed to histamine -induced expression of Toll-like receptor 4 (TLR4). In this study, we examined whether LPS stimulates the H1R expression in human coronary artery endothelial cells (HCAEC) with resultant enhancement of histamine responsiveness. Incubation of HCAEC with LPS (10-1000 ng/ml) resulted in two-fold to fourfold increases in H1R mRNA expression in a time-dependent and concentration-dependent fashion. In contrast, LPS treatment did not affect H2R mRNA expression. The LPS-induced H1R mRNA expression peaked by 4 hr after LPS treatment and remained elevated above the basal level for 20-24 hr. Flow cytometric and Western blot analyses revealed increased expression of H1R protein in LPS-treated cells. The specific binding of [(3)H]pyrilamine to H1R in membrane proteins from LPS-treated HCAEC was threefold higher than the untreated cells. The LPS-induced H1R expression was mediated through TLR4 as gene silencing by TLR4-siRNA and treatment with a TLR4 antagonist inhibited the LPS effect. When HCAEC were pre-treated with LPS for 24 hr, washed and challenged with histamine, 17-, 10- and 15-fold increases in PGI(2), PGE(2) and IL-6 production, respectively, were noted. Histamine-induced enhancement of the synthesis of PGI(2), PGE(2) and IL-6 by LPS-primed HCAEC was completely blocked by an H1R antagonist. The results demonstrate that LPS, through TLR4 activation, up-regulates the expression and function of H1R and amplifies histamine-induced inflammatory responses in HCAEC. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  16. Histamine induces activation of protein kinase D that mediates tissue factor expression and activity in human aortic smooth muscle cells

    Science.gov (United States)

    Hao, Feng; Wu, Daniel Dongwei; Xu, Xuemin

    2012-01-01

    Histamine, an inflammatory mediator, has been shown to influence the pathogenesis of vascular wall cells. However, the molecular basis of its influence is not well understood. Our data reveal that histamine markedly induces protein kinase D (PKD) activation in human aortic smooth muscle cells. PKD belongs to a family of serine/threonine protein kinases, and its function in vascular disease is largely unknown. Our data show that histamine-induced PKD phosphorylation is dependent on the activation of histamine receptor 1 and protein kinase C (PKC). To determine the role of PKD in the histamine pathway, we employed a small-interfering RNA approach to downregulate PKD expression and found that PKD1 and PKD2 are key mediators for expression of tissue factor (TF), which is the key initiator of blood coagulation and is important for thrombosis. Our results show that PKD2 predominantly mediates histamine-induced TF expression via the p38 mitogen-activated protein kinase (MAPK) pathway, whereas PKD1 mediates histamine-induced TF expression through a p38 MAPK-independent pathway. We demonstrate that histamine induces TF expression via the PKC-dependent PKD activation. Our data provide the first evidence that PKD is a new component in histamine signaling in live cells and that PKD has a novel function in the histamine signaling pathway leading to gene expression, as evidenced by TF expression. Importantly, our data reveal a regulatory link from histamine to PKD and TF, providing new insights into the mechanisms of coagulation and the development of atherothrombosis. PMID:23001835

  17. Histamine and mast cell activator compound 48/80 are safe but inefficient systemic adjuvants for gilthead seabream vaccination.

    Science.gov (United States)

    Gómez González, N E; Cabas, I; Montero, J; García Alcázar, A; Mulero, V; García Ayala, A

    2017-07-01

    Histamine has a key role in the regulation of inflammatory and innate immune responses in vertebrates. Gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost of great commercial value, was the first fish species shown to possess histamine-containing mast cells (MCs) at mucosal tissues. MCs are highly abundant in the peritoneal exudate of gilthead seabream and compound 48/80 (Co 48/80), often used to promote MC activation and histamine release, is able to promote histamine release from gilthead seabream MCs in vitro and in vivo. The aim of the present study was to analyze the effect of histamine and Co 48/80 on the immune responses of gilthead seabream. For this purpose, histamine and Co 48/80 were intraperitoneally injected alone or combined with 10 9 heat-killed Vibrio anguillarum cells and their effects on head kidney and peritoneal exudate were analyzed. The results indicated that although histamine and Co 48/80 were both able to alter the percentage of peritoneal exudate and head kidney immune cell types, only Co 48/80 increased reactive oxygen species production by peritoneal leukocytes. In addition, histamine, but not Co 48/80, was able to slightly impair the humoral adaptive immune response, i.e. production of specific IgM to V. anguillarum. Notably, both histamine and Co 48/80 reduced the expression of the gene encoding histamine receptor H2 in peritoneal exudate leukocytes. These results show for the first time in fish that although systemic administration of histamine and Co 48/80 is safe, neither compound can be regarded as an efficient adjuvant for gilthead seabream vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Histamine release from gut mast cells from patients with inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Nolte, Hendrik; Spjeldnæs, Nikolaj; Kruse, Aksel

    1990-01-01

    Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens...... of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative...... colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various...

  20. Impact of fexofenadine, osthole and histamine on peripheral blood mononuclear cell proliferation and cytokine secretion.

    Science.gov (United States)

    Karolina Kordulewska, Natalia; Kostyra, Elżbieta; Matysiewicz, Michał; Cieślińska, Anna; Jarmołowska, Beata

    2015-08-15

    This paper compares results of peripheral blood mononuclear cell (PBMC) incubation with fexofenadine (FXF) and osthole. FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. To our best knowledge, this is the first comparative study on FXF, osthole and histamine cytokine secretion and cytotoxicity in PBMC in vitro cultures using cell proliferation ELISA BrdU. The cultures were treated 12, 42, 48 and 72h with FXF and osthole at 150, 300 and 450ng/ml concentrations and histamine at 50, 100 and 200ng/ml. Our study results confirm that FXF, osthole and histamine exert no cytotoxic effect on PBMCs and that IL-6, IL-10 and TNF-α cytokine secretion following osthole cell stimulation was similar to that by FXF stimulation.This confirms our hypothesis that osthole is a natural histamine antagonist, and can therefore be beneficially applied in antihistamine treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Histamine-enhanced contractile responses of gastric smooth muscle via interstitial cells of Cajal in the Syrian hamster.

    Science.gov (United States)

    Naganuma, S; Shiina, T; Yasuda, S; Suzuki, Y; Shimizu, Y

    2017-11-21

    Gastric motility is controlled by the autonomic and enteric nervous systems and by interstitial cells of Cajal (ICCs). Although histamine is known to be released from enterochromaffin-like cells in the gastric mucosa, its regulatory roles in gastric motility are still controversial. Therefore, we investigated the functional roles of histamine in gastric motility. Stomach preparations from hamsters were used because the stomach of hamsters can be easily separated into the forestomach and the glandular stomach. A whole preparation of the stomach was mounted in a Magnus tube, and mechanical responses were recorded using a force transducer. Exogenous application of histamine had little effect on contractile activity of the glandular stomach. In contrast, the monoamine evoked regular, periodic contractions in the forestomach. An H1 receptor agonist reproduced the contractile responses and an H1 receptor antagonist blocked histamine-evoked contractions. Atropine and tetrodotoxin did not affect the histamine-evoked contractions. Pretreatment with drugs that inhibit the activity of ICCs abolished the effects of histamine. The findings suggest that histamine regulates gastric motility by acting on ICCs via H1 receptors in the hamster. The remarkable ability of histamine to induce rhythmic contractions would be useful for treatment of gastric dysmotility. © 2017 John Wiley & Sons Ltd.

  2. [Shikimic acid inhibits the degranulation and histamine release in RBL-2H3 cells].

    Science.gov (United States)

    Chen, Xianyong; Zheng, Qianqian; Liu, Wei; Yu, Lingling; Wang, Jinling; Li, Shigang

    2017-05-01

    Objective To study the effects of shikimic acid on the proliferation of rat RBL-2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism. Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells treated with 3, 10, 30 μg/mL shikimic acid. Toluidine blue staining was used to observe the degranulation of RBL-2H3 cells. The release of β-hexosaminidase from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 μg/mL C48/80 was determined by substrate assay. ELISA was used to detect the histamine content in the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 μg/mL had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80 concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells compared with the positive control group, the β-hexosaminidase release rate and histamine release were significantly reduced in RBL-2H3 cells treated with shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation of RBL-2H3 cells and reduce histamine release.

  3. Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells.

    Science.gov (United States)

    Hu, Xiufen; Zafar, Mohammad Ishraq; Gao, Feng

    2015-01-01

    We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs) and the influence of lipopolysaccharide (LPS), histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colony-stimulating factor (GM-CSF) alone or with interleukin (IL)-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL). We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA)323-339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-γ production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4- than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days later. IL-13 production was higher in bone marrow DCs generated with GM-CSF than in those generated with GM-CSF + IL-4. OVA-pulsed DCs and OVA-plus-DCL DCs showed increased IL-12 levels. OVA plus LPS increased both IL-10 and interferon-α. Although histamine or histamine receptor-1 antagonists did not influence DC LPS

  4. Nascent histamine induces α-synuclein and caspase-3 on human cells

    Energy Technology Data Exchange (ETDEWEB)

    Caro-Astorga, Joaquín; Fajardo, Ignacio; Ruiz-Pérez, María Victoria; Sánchez-Jiménez, Francisca; Urdiales, José Luis, E-mail: jlurdial@uma.es

    2014-09-05

    Highlights: • Nascent histamine alters cyclin expression pattern. • Nascent histamine increases expression of α-synuclein. • Nascent histamine activates caspase-3. - Abstract: Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein–protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.

  5. Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study

    OpenAIRE

    Bernsand, M; Ericsson, P; Björkqvist, M; Zhao, C -M; Håkanson, R; Norlén, P

    2003-01-01

    Rat stomach ECL cells release histamine in response to gastrin. Submucosal microinfusion of endothelin or adrenaline, known to cause vasoconstriction and gastric lesions, mobilized striking amounts of histamine. While the histamine response to gastrin is sustainable for hours, that to endothelin and adrenaline was characteristically short-lasting (1–2 h).The aims of this study were to identify the cellular source of histamine mobilized by endothelin and adrenaline, and examine the differences...

  6. Dual-Mode Optical Sensing of Histamine at Nanomolar Concentrations in Complex Biological Fluids and Living Cells.

    Science.gov (United States)

    Dey, Nilanjan; Ali, Asfa; Podder, Santosh; Majumdar, Shamik; Nandi, Dipankar; Bhattacharya, Santanu

    2017-09-04

    An easily synthesized fluorescein-based luminescent dye has been utilized for the dual-mode detection of histamine at nanomolar concentrations at pH 7.0 in water. The specific response to histamine was achieved by imidazole-catalyzed 'imine formation' reaction. The protocol was subsequently applied for the estimation of histamine in complex biological milieu such as human blood serum and urine samples. Furthermore, the dose-dependent cellular uptake of histamine and de novo synthesis (by thapsigargin treatment) was visualized in RAW 264.7, a mouse macrophage cell line. We have also developed portable paper strips for rapid, on-site detection of histamine without involving costly instruments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Expression of histamine receptor genes Hrh3 and Hrh4 in rat brain endothelial cells.

    Science.gov (United States)

    Karlstedt, K; Jin, C; Panula, P

    2013-09-01

    Brain vascular endothelial cells express histamine H1 and H2 receptors, which regulate brain capillary permeability. We investigated whether H3 and H4 receptors are also expressed in these cells and may thus play a role in permeability regulation. An immortalized rat brain endothelial cell line RBE4 was used to assess the presence of H3 and H4 receptors. Reverse transcription-PCR (RT-PCR) and sequencing were used to identify the receptor mRNAs. The receptors were stimulated with histamine and immepip, and specific inverse agonists/antagonists ciproxifan and JNJ 7777120 were used to block H3 and H4 receptors, respectively. RT-PCR of mRNA extracted from cultured immortalized RBE4 cells revealed two rat H4 receptor gene (Hrh4) transcripts, one full-length (coding sequence 1173 bp), and one with a 164 bp deletion. Also, two rat H3 receptor gene (Hrh3) isoform mRNAs were expressed in RBE4 cells, and sequencing showed they were the full-length H3 receptor and the 144 bp deletion form. Both histamine and immepip (H3 and H4 receptor agonists) activated the Erk1/2 MAPK pathway in the RBE4 cells and in vivo in brain blood vessels by activating H4 receptors, as the H4 receptor-specific inverse agonists/antagonist JNJ 7777120, but not ciproxifan, H3 receptor antagonist, dose-dependently blocked this effect in RBE4 cells. Both Hrh3 and Hrh4 receptors are expressed in rat brain endothelial cells, and activation of the histamine H4 receptor activates the Erk1/2 cascade. H3 and H4 receptors in endothelial cells are potentially important for regulation of blood-brain barrier permeability, including trafficking of immunocompetent cells. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  8. Utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The role of endogenous adenosine triphosphate (ATP) in histamine release from rat mast cells induced by the ionophore A23187 in vitro has been studied. 2 The amount of histamine released by calcium from rat mast cells primed with the ionophore A23187 was dependent on the ATP content of the mast...... cells. 3 In aerobic experiments a drastic reduction in mast cell ATP content was found during the time when histamine release induced by A23187 takes place. 4 Anaerobic experiments were performed with metabolic inhibitors (antimycin A, oligomycin, and carbonyl cyanide p...... The observations are consistent with the view that energy requiring processes are involved in ionophore-induced histamine release from rat mast cells although part of the ATP reduction in the aerobic experiments may be due to an uncoupling effect of calcium on the oxidative phosphorylation....

  9. Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

    Science.gov (United States)

    Liu, Shao-Cheng; Lin, Chun-Shu; Chen, Shyi-Gen; Chu, Yueng-Hsiang; Lee, Fei-Peng; Lu, Hsuan-Hsuan; Wang, Hsing-Won

    2017-02-01

    Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

  10. Prostaglandin E2Inhibits Histamine-Evoked Ca2+Release in Human Aortic Smooth Muscle Cells through Hyperactive cAMP Signaling Junctions and Protein Kinase A.

    Science.gov (United States)

    Taylor, Emily J A; Pantazaka, Evangelia; Shelley, Kathryn L; Taylor, Colin W

    2017-11-01

    In human aortic smooth muscle cells, prostaglandin E 2 (PGE 2 ) stimulates adenylyl cyclase (AC) and attenuates the increase in intracellular free Ca 2+ concentration evoked by activation of histamine H 1 receptors. The mechanisms are not resolved. We show that cAMP mediates inhibition of histamine-evoked Ca 2+ signals by PGE 2 Exchange proteins activated by cAMP were not required, but the effects were attenuated by inhibition of cAMP-dependent protein kinase (PKA). PGE 2 had no effect on the Ca 2+ signals evoked by protease-activated receptors, heterologously expressed muscarinic M3 receptors, or by direct activation of inositol 1,4,5-trisphosphate (IP 3 ) receptors by photolysis of caged IP 3 The rate of Ca 2+ removal from the cytosol was unaffected by PGE 2 , but PGE 2 attenuated histamine-evoked IP 3 accumulation. Substantial inhibition of AC had no effect on the concentration-dependent inhibition of Ca 2+ signals by PGE 2 or butaprost (to activate EP 2 receptors selectively), but it modestly attenuated responses to EP 4 receptors, activation of which generated less cAMP than EP 2 receptors. We conclude that inhibition of histamine-evoked Ca 2+ signals by PGE 2 occurs through "hyperactive signaling junctions," wherein cAMP is locally delivered to PKA at supersaturating concentrations to cause uncoupling of H 1 receptors from phospholipase C. This sequence allows digital signaling from PGE 2 receptors, through cAMP and PKA, to histamine-evoked Ca 2+ signals. Copyright © 2017 by The Author(s).

  11. Mast cells and histamine alter intestinal permeability during malaria parasite infection.

    Science.gov (United States)

    Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley

    2016-03-01

    Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

  12. Combined Blockade of the Histamine H1 and H4 Receptor Suppresses Peanut-Induced Intestinal Anaphylaxis by Regulating Dendritic Cell Function

    Science.gov (United States)

    Wang, Meiqin; Han, Junyan; Domenico, Joanne; Shin, Yoo Seob; Jia, Yi; Gelfand, Erwin W.

    2016-01-01

    Background Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis. Objectives To determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy. Methods Balb/c mice were sensitized and challenged to peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120. Bone marrow-derived DCs (BMDCs) were adoptively transferred to non-sensitized WT mice. Symptoms, intestinal inflammation, mesenteric lymph node and intestine mucosal DCs were assessed. Effects of the drugs on DC chemotaxis, calcium mobilization, and antigen-presenting cell function were measured. Results Treatment with loratadine or JNJ7777120 individually partially suppressed development of diarrhea and intestinal inflammation and decreased the numbers of DCs in the mesenteric lymph nodes and lamina propria. Combined treatment with both drugs prevented development of diarrhea and intestinal inflammation. In vitro, the combination suppressed DC antigen presenting cell function to T helper cells and DC calcium mobilization and chemotaxis to histamine. Conclusion Blockade of both H1R and H4R in the challenge phase had additive effects in preventing the intestinal consequences of peanut sensitization and challenge. These effects were mediated through limitation of mesenteric lymph node and intestinal DC accumulation and function. Identification of this histamine-H1R/H4R-DC-CD4+ T cell axis provides new insights into the development of peanut-induced intestinal allergic responses and for prevention and treatment of peanut allergy. PMID:27059534

  13. Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, F; Middleton, M; Fode, K

    2005-01-01

    Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2...... with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days...... per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both...

  14. Distinct signalling pathways of murine histamine H1- and H4-receptors expressed at comparable levels in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Silke Beermann

    Full Text Available Histamine (HA is recognized by its target cells via four G-protein-coupled receptors, referred to as histamine H1-receptor (H1R, H2R, H3R, and H4R. Both H1R and H4R exert pro-inflammatory functions. However, their signal transduction pathways have never been analyzed in a directly comparable manner side by side. Moreover, the analysis of pharmacological properties of the murine orthologs, representing the main targets of pre-clinical research, is very important. Therefore, we engineered recombinant HEK293 cells expressing either mouse (mH1R or mH4R at similar levels and analyzed HA-induced signalling in these cells. HA induced intracellular calcium mobilization via both mH1R and mH4R, with the mH1R being much more effective. Whereas cAMP accumulation was potentiated via the mH1R, it was reduced via the mH4R. The regulation of both second messengers via the H4R, but not the H1R, was sensitive to pertussis toxin (PTX. The mitogen-activated protein kinases (MAPKs ERK 1/2 were massively activated downstream of both receptors and demonstrated a functional involvement in HA-induced EGR-1 gene expression. The p38 MAPK was moderately activated via both receptors as well, but was functionally involved in HA-induced EGR-1 gene expression only in H4R-expressing cells. Surprisingly, in this system p38 MAPK activity reduced the HA-induced gene expression. In summary, using this system which allows a direct comparison of mH1R- and mH4R-induced signalling, qualitative and quantitative differences on the levels of second messenger generation and also in terms of p38 MAPK function became evident.

  15. Vascular Effects of Histamine

    African Journals Online (AJOL)

    olayemitoyin

    Endogenous histamine is a classical inflammatory and immunological mediator mainly produced by mast cells and basophils and plays a role in allergic response .... Black J.W., Duncan W.A.M., Durant C.J., Ganellin. C.R. and Parsons M.E. (1972): Definition and antagonism of histamine H1 receptors. Nature 236: 385-390.

  16. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    of proliferation and angiogenesis. Specific histamine receptors have been identified on the surface of bone marrow cells, immune competent cells, endothelial cells, fibroblasts, and also on malignant cells. This has prompted research in regulation by specific histamine receptor agonists and antagonists. Results...... from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  17. Involvement of glial cells in the nociceptive behaviors induced by a high-dose of histamine administered intrathecally.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-02-25

    The involvement of spinal glial cells in the nociceptive behaviors induced by 1600 pmol of histamine was determined in mice. Histamine injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. pretreatment with the glial cell inhibitor DL-fluorocitric acid or minocycline. In Western blot analysis using lumber spinal cords, i.t. treatment with histamine increased the phosphorylation of the NR1 subunit of N-methyl-D-aspartate (NMDA) receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with DL-fluorocitric acid or minocycline. We have previously reported that the nociceptive behaviors induced by 1600 pmol of histamine were significantly suppressed by the i.t. co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine (MK-801), an ion channel blocker of NMDA receptors, or agmatine, an antagonist for the polyamine recognition site on the NR1 subunit of NMDA receptors. In the present study, the increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was also abolished by i.t. co-administration of agmatine or MK-801. The present results suggest that histamine at 1600 pmol elicits nociceptive behaviors by stimulating the polyamine recognition site on the NR1 subunit of NMDA receptors on spinal glial cells. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease

    Directory of Open Access Journals (Sweden)

    Sherin Saheera

    2017-10-01

    Full Text Available Background Cardiac stem cells (CSCs play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. Methods To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Results Functional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment. Discussion As anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of

  19. Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells

    Science.gov (United States)

    Nagai, Yasuhiro; Tanaka, Yukinori; Kuroishi, Toshinobu; Sato, Ryutaro; Endo, Yasuo; Sugawara, Shunji

    2012-01-01

    Natural killer (NK) group 2D (NKG2D) is a key activating receptor expressed on NK cells, whose interaction with ligands on target cells plays an important role in tumorigenesis. However, the effect of histamine on NKG2D ligands on tumour cells is unclear. Here we showed that human monocytic leukaemia THP-1 cells constitutively express MHC class I-related chain A (MICA) and UL16-binding protein 1 on their surface, and incubation with histamine reduced the expression in a dose-dependent and time-dependent manner as assessed by flow cytometry. Interferon-γ augmented the surface expression of the NKG2D ligands, and this augmentation was significantly attenuated by histamine. The histamine H1 receptor (H1R) agonist 2-pyridylethylamine and H2R agonist dimaprit down-regulated the expression of NKG2D ligands, and activation of H1R and H2R signalling by A23187 and forskolin, respectively, had the same effect, indicating that the histamine-induced down-regulation of NKG2D ligands is mediated by H1R and H2R. Quantitative reverse transcription-PCR showed that mRNA levels of the NKG2D ligands and relevant microRNAs were not significantly changed by histamine. Histamine down-regulated the surface expression of endoplasmic reticulum protein 5, and inhibition of matrix metalloproteinases did not impair this down-regulation, indicating that proteolytic shedding was not involved. Instead, pharmacological inhibition of protein transport and proteasome abrogated it, and histamine enhanced ubiquitination of MICA. Furthermore, histamine treatment significantly reduced susceptibility to NK cell-mediated cytotoxicity. These results suggest that histamine down-regulates NKG2D ligands through the activation of an H1R- and H2R-mediated ubiquitin–proteasome pathway and consequently reduces susceptibility to NK cells. PMID:22304689

  20. Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells.

    Science.gov (United States)

    Nagai, Yasuhiro; Tanaka, Yukinori; Kuroishi, Toshinobu; Sato, Ryutaro; Endo, Yasuo; Sugawara, Shunji

    2012-05-01

    Natural killer (NK) group 2D (NKG2D) is a key activating receptor expressed on NK cells, whose interaction with ligands on target cells plays an important role in tumorigenesis. However, the effect of histamine on NKG2D ligands on tumour cells is unclear. Here we showed that human monocytic leukaemia THP-1 cells constitutively express MHC class I-related chain A (MICA) and UL16-binding protein 1 on their surface, and incubation with histamine reduced the expression in a dose-dependent and time-dependent manner as assessed by flow cytometry. Interferon-γ augmented the surface expression of the NKG2D ligands, and this augmentation was significantly attenuated by histamine. The histamine H1 receptor (H1R) agonist 2-pyridylethylamine and H2R agonist dimaprit down-regulated the expression of NKG2D ligands, and activation of H1R and H2R signalling by A23187 and forskolin, respectively, had the same effect, indicating that the histamine-induced down-regulation of NKG2D ligands is mediated by H1R and H2R. Quantitative reverse transcription-PCR showed that mRNA levels of the NKG2D ligands and relevant microRNAs were not significantly changed by histamine. Histamine down-regulated the surface expression of endoplasmic reticulum protein 5, and inhibition of matrix metalloproteinases did not impair this down-regulation, indicating that proteolytic shedding was not involved. Instead, pharmacological inhibition of protein transport and proteasome abrogated it, and histamine enhanced ubiquitination of MICA. Furthermore, histamine treatment significantly reduced susceptibility to NK cell-mediated cytotoxicity. These results suggest that histamine down-regulates NKG2D ligands through the activation of an H1R- and H2R-mediated ubiquitin-proteasome pathway and consequently reduces susceptibility to NK cells. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  1. Diallyl sulfide as a potential dietary agent to reduce TNF-α- and histamine-induced proinflammatory responses in A7r5 cells.

    Science.gov (United States)

    Ho, Cheng-Ying; Weng, Chia-Jui; Jhang, Jhih-Jia; Cheng, Yu-Ting; Huang, Shang-Ming; Yen, Gow-Chin

    2014-05-01

    Oxidative stress-aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor-alpha (TNF-α)- or histamine-induced inflammation in rat aortic smooth muscle A7r5 cells. A7r5 cells were coincubated with DAS before exposure to TNF-α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF-α-induced A7r5 cells by attenuating the TNF-α receptor complex through the dissociation of the TNF receptor-associated death domain and TNF receptor-associated factor 2. Moreover, DAS inhibited histamine-induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor-erythroid 2-related factor 2-related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin-1β and TNF-α through the inhibition of ROS-induced PI3K/Akt and the downstream NF-κB and activator protein-1. Our results demonstrate that DAS is a potential phytochemical to inhibit TNF-α- and histamine-induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress-induced inflammation of the airway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Resolvin D1 and Aspirin-Triggered Resolvin D1 Regulate Histamine-stimulated Conjunctival Goblet Cell Secretion

    Science.gov (United States)

    Li, Dayu; Hodges, Robin R.; Jiao, Jianwei; Carozza, Richard B.; Shatos, Marie A.; Chiang, Nan; Serhan, Charles N.; Dartt, Darlene A.

    2013-01-01

    Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. Since resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors, as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca2+] ([Ca2+]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca2+]i and activation of extracellular regulated protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies. PMID:23462912

  3. A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

    Directory of Open Access Journals (Sweden)

    Chen Eric Y

    2012-01-01

    Full Text Available Abstract Background Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs, a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. Results TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER were responsible for the sustained elevation of [Ca2+]C and histamine secretion. Conclusion Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.

  4. Role of protein phosphatases inhibitors on the histamine release and the functional desensitization in human lung mast cells

    Directory of Open Access Journals (Sweden)

    Reza Bastan

    2014-01-01

    Full Text Available Background: The β2-adrenoceptor agonist, isoprenaline, is an effective inhibitor of histamine release from human lung mast cells (HLMC. Since phosphorylations of the β2-adrenoceptors are probably important in inducing desensitization, we sought to investigate the importance of phosphorylation events by targeting protein phosphatases (PPs in mast cells. To this end, the effects of the inhibitor of on the functional desensitization of β-adrenoceptor-mediated responses in mast cells were investigated. Materials and Methods: In this study the effects of PP inhibitors on the inhibition of histamine release from HLMC, on β-agonists in mast cells and on desensitization were investigated. Results: Long-term exposure of mast cells to both isoprenaline and salbutamol substantially reduced the extent to which isoprenaline inhibited histamine release. Pretreatments of up to 24 h with inhibitors alone had no effect on immunoglobulin E-mediated histamine release. Shorter (≤4 h pretreatments had little effect on the activity of isoprenaline and salbutamol to inhibit histamine release from mast cells. Conclusion: Collectively, these data suggest that PP has an important role in regulating mast cell β2-adrenoceptors.

  5. Diamine Oxidase from White Pea (Lathyrus sativus) Combined with Catalase Protects the Human Intestinal Caco-2 Cell Line from Histamine Damage.

    Science.gov (United States)

    Jumarie, Catherine; Séïde, Marilyne; Marcocci, Lucia; Pietrangeli, Paola; Mateescu, Mircea Alexandru

    2017-07-01

    Diamine oxidase (DAO) administration has been proposed to treat certain gastrointestinal dysfunctions induced by histamine, an immunomodulator, signaling, and pro-inflammatory factor. However, H 2 O 2 resulting from the oxidative deamination of histamine by DAO may be toxic. The purpose of this study was to investigate to which extent DAO from white pea (Lathyrus sativus), alone or in combination with catalase, may modulate histamine toxicity in the human intestinal Caco-2 cell line. The results show that histamine at concentrations higher than 1 mM is toxic to the Caco-2 cells, independently of the cell differentiation status, with a LC 50 of ≅ 10 mM following a 24-h exposure. Depending on its concentration, DAO increased histamine toxicity to a greater extent in differentiated cells compared to undifferentiated cultures. In the presence of catalase, the DAO-induced increase in histamine toxicity was completely abolished in the undifferentiated cells and only partially decreased in differentiated cells, showing differences in the sensitivity of Caco-2 cells to the products resulting from histamine degradation by DAO (H 2 O 2 , NH 3 , or imidazole aldehyde). It appears that treatment of food histaminosis using a combination of vegetal DAO and catalase would protect against histamine toxicity and prevent H 2 O 2 -induced damage that may occur during histamine oxidative deamination.

  6. The Effect of Histamine on Dendritic Cells Pulsed with Myelin Proteins and Autologous T Cell Response in Vitro

    Directory of Open Access Journals (Sweden)

    H Mohebalian

    2013-07-01

    Full Text Available Abstract Background & aim: The role of dendritic cells in the immune responses has led to the application of these cells in autoimmune diseases such as multiple sclerosis. The aim of this study was to investigate the effect of histamine on dendritic cells pulsed with myelin proteins and autologous T cell response in vitro. Methods: In this experimental study, blood samples were taken from 5 volunteers. Subsequently, peripheral blood mononuclear cells were isolated by using Phicole Hypaque. Using GM-CSF cytokine and IL-4, dendritic cells were produced from peripheral blood and then stimulated with MBP in the presence and without histamine in control and treated group to be matured. The CD14+ and surface markers of resulted DC were evaluated by Flowcytometry. The levels of cytokines IL-10 and IL-12 in dendritic cells culture and IL-4, and IFN-γ in both cultured dendritic cells and antilogous T cells were obtained. And then the proliferation of T lymphocytes in the treatment and control groups were compared. The collected data was analyzed by Student's t-test and ANOVA. Results: In the treatment group, the expression of CD83 (from 3/15 to 5/24% and HLA-DR (from 3/26 to 38% was significantly higher than the control group (P> 0.05. The expression of CD14 exhibited no change. The secretion of IL-10 increased and IL-12 showed a decrease. The secretion of IL-4/IFN- ᵞ showed an increase in treated group than the control group (P ˂ 0/05. Conclusion: Histamine deviation with immune responses from TH1/TH17 to the TH2 in an experimental model of MS can be used as a new method of DC-based vaccines which may be useful in treating this disease. Key words: Denderitic Cells, Myelin Basic Protein (MBP, Histamine, Multiple sclerosis (MS

  7. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Science.gov (United States)

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Ligands for histamine H3 receptors modulate cell proliferation and migration in rat oxyntic mucosa

    OpenAIRE

    Morini, Giuseppina; Grandi, Daniela; Schunack, Walter

    2002-01-01

    (R)-α-methylhistamine, a selective agonist of histamine H3 receptors, promotes mucus secretion and increases the number and volume of mucus-secreting cells. The hypothesis that the increased number of mucous cells could reside in an alteration of homeostasis in the gastric epithelium was investigated.(R)-α-methylhistamine was administered to rats 1 h (10–100 mg kg−1 by intragastric and by intraperitoneal route) and 24 h (100 mg kg−1 by intragastric route) prior to killing. The (S)-isomer of α...

  9. Short-term desensitization of the histamine H1 receptor in human HeLa cells : involvement of protein kinase C dependent and independent pathways

    NARCIS (Netherlands)

    Smit, M J; Bloemers, S M; Leurs, R; Tertoolen, L G; Bast, A; de Laat, S W; Timmerman, H

    1992-01-01

    1. In this study we have investigated the effects of short-term exposure of cells to histamine on the subsequent H1 receptor responsiveness in HeLa cells, using Ca2+ fluorescence microscopy and video digital imaging. 2. In HeLa cells, histamine (100 microM) induces an immediate H1 receptor-mediated

  10. Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely...... related to the histamine release process and not to an uncoupling of oxidative phosphorylation by an increased concentration of cytosol Ca2+. The ATP content of the cells was not restored within the 2 h of observation. No inhibition of lactate production from mast cells exposed to antigen in the presence...

  11. Functional characterization of histamine H4 receptor on human mast cells.

    Science.gov (United States)

    Jemima, E Angel; Prema, A; Thangam, E Berla

    2014-11-01

    Among the four different types of histamine receptors (H1-H4), H4R is predominantly expressed in immune cells and involved in immunomodulatory response. Here, in this study we determined the expression of H4R in human mast cells (HMC-1, LAD-2 and primary cord blood derived CD34+ human mast cells) and characterized its functional properties. Interestingly, we found that human mast cells responded to both histamine (natural ligand) and 4-methylhistamine (selective H4R agonist) for sustained intracellular calcium mobilization, degranulation and cytokine production. However, only histamine induced the release of cAMP, but 4-methylhistamine down regulates cAMP indicating that H4R mediates its effect through Gαi/o protein and H1R via Gαq protein. Furthermore, both histamine and 4-methylhistamine induced the production of cysteinyl leukotrienes and LTB4. Using human inflammation antibody array membrane, we found that H4R induced the expression of various inflammatory proteins, involving pro-inflammatory cytokines and chemokines and these are TGF-β1, TNF-α, TNF-β, PDGF-BB, TIMP-2, M-CSF, IP-10, IL-16, IL-6, IL-3, IL-10, MIP-1α, IL-1α, ICAM-1, Eotaxin-2, RANTES, IL-8, MCP-1, and IL-6sR. We also quantified the level of various inflammatory cytokines produced by human mast cells through H4R. It was observed that, the production level of Th2 cytokines IL-4(401.34 pg/ml), IL-5 (64.21 pg/ml) and IL-13 (1044 pg/ml) and classical proinflammatory cytokines IL-6 (221.27 pg/ml) and IL-1β (34.24 pg/ml) and chemokines MCP-1(106 pg/ml) and IL-8 (818.32 pg/ml). Furthermore, activation of H4R caused the phosphorylation of ERK and PI3K in a time dependent manner. Taken together these data demonstrate that, the activation of H4R in human mast cells produced not only inflammatory mediators that are associated with allergic reactions but also other inflammatory conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Rosae Multiflorae Fructus Hot Water Extract Inhibits a Murine Allergic Asthma Via the Suppression of Th2 Cytokine Production and Histamine Release from Mast Cells.

    Science.gov (United States)

    Song, Chang Ho; Bui, Thi Tho; Piao, Chun Hua; Shin, Hee Soon; Shon, Dong-Hwa; Han, Eui-Hyeog; Kim, Hyoung Tae; Chai, Ok Hee

    2016-09-01

    Mast cell-mediated anaphylactic reactions are involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, Rosae Multiflorae fructus (RMF) is known to have potent antioxidative, analgesic, and anti-inflammatory activities and to have no obvious acute toxicity. However, its specific effect on asthma is still unknown. In this study, we evaluated whether or not RMF hot water extracts (RMFW) could inhibit ovalbumin (OVA)-induced allergic asthma and evaluated compound 48/80-induced mast cell activation to elucidate the mechanisms of asthma inhibition by RMFW. Oral administration of RMFW decreased the number of eosinophils and lymphocytes in the lungs of mice challenged by OVA and downregulated histological changes such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. In addition, RMFW significantly reduced T helper 2 cytokines, TNF-α, IL-4, and IL-6 levels in the BAL fluid of mice challenged by OVA. Moreover, RMFW suppressed compound 48/80-induced rat peritoneal mast cell degranulation and inhibited histamine release from mast cells induced by compound 48/80 in a dose-dependent manner. These results suggest that RMFW may act as an antiallergic agent by inhibitingTh2 cytokine production from Th2 cells and histamine release from mast cells, and could be used as a therapy for patients with Th2-mediated or mast cell-mediated allergic diseases.

  13. Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells.

    Science.gov (United States)

    Ku, Hye Jin; Kim, Hye Young; Kim, Hyeong Hoe; Park, Hee Ju; Cheong, Jae Hun

    2014-01-07

    To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation. HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay. Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues. HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.

  14. Histamine is required during neural stem cell proliferation to increase neuron differentiation.

    Science.gov (United States)

    Rodríguez-Martínez, G; Velasco, I; García-López, G; Solís, K H; Flores-Herrera, H; Díaz, N F; Molina-Hernández, A

    2012-08-02

    Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. We have previously shown that HA is able to increase neuronal differentiation of neural stem cells (NSCs) in vitro, by activating the histamine type 1 receptor. However the mechanism(s) by which HA has a neurogenic effect on NSCs has not been explored. Here we explore how HA is able to increase neuron phenotype. Cortex neuroepithelium progenitors were cultured and at passage two treatments with 100 μM HA were given during cell proliferation and differentiation or only during differentiation. Immunocytochemistry was performed on differentiated cultures to detect mature neurons. To explore the expression of certain important transcriptional factors involved on asymmetric cell division and commitment, RT-PCR and qRT-PCR were performed. Results indicate that HA is required during cell proliferation in order to increase neuron differentiation and suggest that this amine increases neuron commitment during the proliferative phase probably by rising prospero1 and neurogenin1 expression. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Ethacrynic acid inhibition of histamine release from rat mast cells: effect on cellular ATP levels and thiol groups

    DEFF Research Database (Denmark)

    Johansen, Torben

    1983-01-01

    The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose....... Furthermore, the inhibition of histamine release occurred mainly through interaction with thiol groups, although inhibition of cellular energy production may have been an additional mechanism....... as well as in presence of 2-deoxyglucose. A23187-induced histamine release was inhibited by ethacrynic acid, and this inhibition was completely reversed by dithiothreitol. These observations may indicate that ethacrynic acid inhibits glycolytic and respiratory energy production in rat mast cells...

  16. Histamine affects interleukin-4, interleukin-5, and interferon-gamma production by human T cell clones from the airways and blood

    NARCIS (Netherlands)

    Krouwels, F. H.; Hol, B. E.; Lutter, R.; Bruinier, B.; Bast, A.; Jansen, H. M.; Out, T. A.

    1998-01-01

    High levels of histamine can be found in the airways of asthma patients. This study describes the effects of histamine on anti-CD3-induced production of IL-4, IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and healthy subjects. T cell clones were obtained from

  17. Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

    Science.gov (United States)

    Sena, C M; Rosário, L M; Parker, P J; Patel, V; Boarder, M R

    1996-03-01

    In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin

  18. Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

    DEFF Research Database (Denmark)

    Clementsen, P; Bisgaard, H; Pedersen, M

    1989-01-01

    was found to release histamine from cells from 7 of the 13 individuals and influenza A virus in 3 of 5 persons. Furthermore, Staph, aureus stimulated the BAL-cells to release leukotriene B4 in 7 of 11 subjects, whereas no release was found by influenza A virus in 7 examined persons. When cells from 4......Mediator release was examined from superficially lying cells in the airway epithelium obtained by bronchoalveolar lavage (BAL) in 13 non-atopic individuals. The BAL-cells were incubated (20 min, 37 degrees C) with Staphylococcus (Staph.) aureus or with human influenza A virus Staph. aureus...... with entrance of allergens and other insulting particles, and leukotriene B4 facilitates airway inflammation....

  19. Histamine modulates microglia function

    Science.gov (United States)

    2012-01-01

    Background Histamine is commonly acknowledged as an inflammatory mediator in peripheral tissues, leaving its role in brain immune responses scarcely studied. Therefore, our aim was to uncover the cellular and molecular mechanisms elicited by this molecule and its receptors in microglia-induced inflammation by evaluating cell migration and inflammatory mediator release. Methods Firstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR analysis, immunocytochemistry and Western blotting. Then, we evaluated the role of histamine in microglial cell motility by performing scratch wound assays. Results were further confirmed using murine cortex explants. Finally, interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by ELISA measurements to determine the role of histamine on the release of these inflammatory mediators. Results After 12 h of treatment, 100 μM histamine and 10 μg/ml histamine-loaded poly (lactic-co-glycolic acid) microparticles significantly stimulated microglia motility via H4R activation. In addition, migration involves α5β1 integrins, and p38 and Akt signaling pathways. Migration of microglial cells was also enhanced in the presence of lipopolysaccharide (LPS, 100 ng/ml), used as a positive control. Importantly, histamine inhibited LPS-stimulated migration via H4R activation. Histamine or H4R agonist also inhibited LPS-induced IL-1β release in both N9 microglia cell line and hippocampal organotypic slice cultures. Conclusions To our knowledge, we are the first to show a dual role of histamine in the modulation of microglial inflammatory responses. Altogether, our data suggest that histamine per se triggers microglia motility, whereas histamine impedes LPS-induced microglia migration and IL-1β release. This last datum assigns a new putative anti-inflammatory role for

  20. The effect of histamine on the oxidative burst of HL60 cells before and after exposure to reactive oxygen species.

    NARCIS (Netherlands)

    Ching, T.L.; Koelemij, J.G.; Bast, A.

    1995-01-01

    During an inflammation neutrophils are stimulated to produce reactive oxygen species (ROS). These ROS induce the release of histamine from mast cells, which are also present at the inflammation site. In this study dibutyryl cAMP differentiated HL60 cells are used as a model for human neutrophils.

  1. Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely re...

  2. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

    Science.gov (United States)

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben-induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not. Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. PMID:12770943

  3. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    Science.gov (United States)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  4. Allergic inflammation is augmented via histamine H4 receptor activation: The role of natural killer cells in vitro and in vivo.

    Science.gov (United States)

    Ehling, Sarah; Roßbach, Kristine; Dunston, Stanley M; Stark, Holger; Bäumer, Wolfgang

    2016-08-01

    Natural Killer cells (NK cells) are identified as pivotal mediators in allergic skin diseases and accumulate in lesions of atopic dermatitis (AD) patients. Histamine levels are increased in these lesions and histamine is involved in chemotaxis in dendritic cells and NK cells. The aim of this study was to determine if the histamine H4 receptor (H4R) mediates NK cell chemotaxis and whether it influences interplay between NK cells and dendritic cells during the early phase of allergic inflammation. Chemotactic function of the H4R as well as the influence of the H4R on the cytokine profile of an NK cell-dendritic cell co-culture was studied in vitro. The effect of H4R activation on NK cell migration, NK cell-dendritic cell interaction and cytokine levels in the skin was further characterized in the murine TDI model of allergic dermatitis. Additionally, the impact of the H4R on dermal NK cells was determined in the ovalbumin (OVA)- induced allergic dermatitis model, comparing wild type and H4R knockout mice. The selective H4R agonist ST-1006 induced NK cell chemotaxis in vitro, which was inhibited with the H4R antagonist JNJ7777120. In vivo, mice treated with TDI plus ST-1006 topically onto the ear, showed significantly enhanced ear swelling and an increased number of NK cells compared to just allergen challenged ears. CCL17 levels in the ear were also significantly increased 8h after allergen challenge. Histology revealed that the main source for increased CCL17 were dendritic cells. These effects could be blocked using the H4R antagonist JNJ7777120. In the chronic model of allergic dermatitis, OVA induced NK cell migration into lesional skin sites. The number of NK cells was lower in OVA-sensitized H4R knockout mice compared to wild type mice. These results identify the H4R as a new target controlling NK cell migration and NK cell-dendritic cell interaction in the skin during early allergic inflammation. These results further suggest that blocking the H4R in the skin

  5. Allergy, Histamine and Antihistamines.

    Science.gov (United States)

    Church, Martin K

    2017-01-01

    This chapter concentrates on the role in allergic disease of histamine acting on H 1 -receptors. It is clear that allergy has its roots in the primary parasite rejection response in which mast cell-derived histamine creates an immediate hostile environment and eosinophils are recruited for killing. This pattern is seen in allergic rhinitis where the early events of mucus production and nasal itching are primarily histamine mediated whereas nasal blockage is secondary to eosinophil infiltration and activation. In asthma, the role of histamine is less clear. Urticaria is characterized by mast cell driven pruritic wheal and flare-type skin reactions that usually persist for less than 24 h. Although the events leading to mast cell degranulation have been unclear for many years, it is now becoming evident that urticaria has an autoimmune basis. Finally, the properties of first- and second-generation H 1 -antihistamines and their role in allergic is discussed.

  6. Histamine Promotes the Development of Monocyte-Derived Dendritic Cells and Reduces Tumor Growth by Targeting the Myeloid NADPH Oxidase

    Science.gov (United States)

    Wiktorin, Hanna G.; Lenox, Brianna; Ewald Sander, Frida; Aydin, Ebru; Aurelius, Johan; Thorén, Fredrik B.; Ståhlberg, Anders; Hermodsson, Svante; Hellstrand, Kristoffer

    2015-01-01

    The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase–derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91phox−/−) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer. PMID:25870245

  7. Histamine modulates cell growth, reactive oxygen species production and activity of antioxidant enzymes in human cell lines

    International Nuclear Information System (INIS)

    Medina, V.; Cricco, G.; Garbarino, G.; Nunez, M.; Martin, G.; Cocca, C.; Bergoc, R.M.; Rivera, E.S.

    2004-01-01

    Full text: In the present work, the capacity of Histamine (HA) to modulate cell proliferation and ROS production as well as the receptors involved in this response was investigated. Mammary normal (HBL-100) and malignant cell lines (MDA-MB-231, MCF- 7) was employed. The levels of the free radicals superoxide (O 2 - ) and hydrogen peroxide (H 2 O 2 ) and intracellular HA content were determined by flow cytometry. The activity of antioxidant enzymes, super-oxide dismutase (SOD) and catalase (CAT) were determined by kinetic spectrophotometric techniques. Cell proliferation was evaluated by the clonogenic assay. Cell lines presented intracellular levels of HA directly correlated with their malignancy. In MDA-MB-231, HA via H 2 R increased cAMP levels (EC 50 0.45 μM) producing in turn a significant inhibition on cell proliferation (p 1 R, stimulated cell growth. H 2 O 2 levels resulted inversely correlated with cell proliferation while O 2 - remained unchanged. Furthermore, HA significantly modified the activity of SOD and CAT. In normal HBL-100, HA modulates cell proliferation but in exactly the opposite range of doses. The effect on cell growth was inversely correlated with H 2 O 2 levels. The present data indicate that histamine can modulate cell proliferation via H 1 R and H 2 R. This effect is exerted in part by the modulation of antioxidant enzymes and ROS production. (author)

  8. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

    OpenAIRE

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs).In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release.In RPMCs pretreated with a protein kinase C (PKC) activator (p...

  9. Ouabain enhancement of compound 48/80 induced histamine secretion from rat peritoneal mast cells: dependence on extracellular sodium

    DEFF Research Database (Denmark)

    Knudsen, T; Bertelsen, Niels Haldor; Johansen, Torben

    1992-01-01

    a measure of the Na(+)-K+ pump activity of the cells. Ouabain caused an immediate inhibition of the pump activity and a time-dependent increase in histamine secretion in the absence of extracellular calcium. No effect on the secretion was observed in the presence of calcium. The effect of ouabain......-free medium, the pump activity was inhibited and the enhancement by ouabain of the secretion of histamine was blocked. A less marked inhibition of the pump was found in a calcium-free medium containing magnesium. The inhibition exerted by magnesium was concentration-dependent (0-5 mM) as was the counteraction...

  10. Histamine and Histamine Receptors in Allergic Dermatitis.

    Science.gov (United States)

    Ohtsu, Hiroshi; Seike, Masahiro

    2017-01-01

    In this chapter we will first introduce the pathophysiological process of several skin diseases including allergic dermatitis, a common skin disease, including chronic allergic contact dermatitis (CACD), and atopic dermatitis (AD). In CACD and AD patients, repeated skin exposure to antigens contributes to the development of chronic eczematous lesions. Repeated application of haptens on mice allows emulation of the development of CACD in humans. Further, we will focus on H1, H2, and H4 histamine receptors and their effects on CACD and AD. Histamine-deficient mice, with a knockout histidine decarboxylase (HDC) gene, were used to investigate the role of histamine in CACD and AD. Histamine induces infiltration of inflammatory cells, including mast cells and eosinophils, and elevates Th2 cytokine levels in CACD. Histamine promotes the development of eczematous lesions, elevates IgE serum levels, and induces scratching behavior in CACD. The administration of H1 or H4 receptor antagonists was effective to ameliorate these symptoms in murine CACD models. The combination of H1 and H4 receptor antagonists is a potential therapeutic target for chronic inflammatory skin diseases such as CACD and AD, since combined therapy proved to be more effective than monotherapy.

  11. Lack of role for mononuclear cell-derived histamine releasing factors in occupational asthma due to western red cedar.

    Science.gov (United States)

    Frew, A J; Chan, H; Chan-Yeung, M

    1993-10-01

    Occupational asthma due to Western Red Cedar (WRCA) is attributed to sensitization to plicatic acid (PA), but does not appear to be dependent on PA-specific IgE antibodies. Exposure to PA induces histamine release in vivo and in vitro, so if IgE is not important, other mechanisms of histamine release must presumably operate in WRCA. To explore the possible role of histamine-releasing factors in WRCA, peripheral blood mononuclear cells were obtained and cultured with PA, PA-albumin conjugate plicatic acid-human serum albumin (PA-HSA), grass pollen or Concanavalin A using a standard histamine releasing factor (HRF) generation protocol. Supernatants were dialysed to remove endogenous histamine and then assayed for histamine releasing activity using human basophils as targets and a Con A-induced bulk supernatant as an internal HRF standard. In contrast to some previous reports, spontaneous HRF release from the peripheral blood mononuclear cells (PBMC) of WRCA patients (n=9) and atopic asthmatic subjects (n=5) was not elevated compared with the non-asthmatic controls (n=11; five atopic and six non-atopic). Both PA and PA-HSA induced the production of small amounts of HRF by PBMC of WRCA patients, but a similar degree of HRF generation was also observed in PBMC from the atopic asthmatic, atopic nonasthmatic, and non-atopic subjects. In contrast, grass pollen induced the production of HRF by PBMC from the subjects with positive skin tests to grass pollen but not by PBMC of non-atopic subjects, confirming that our methods and assay were capable of detecting antigen-specific HRF production. Since neither PA nor PA-HSA induced significantly elevated HRF production from PBMC of WRCA patients, it seems unlikely that PA-induced HRFs play a substantial role in the pathogenesis of WRCA.

  12. The suppression of IgE-mediated histamine release from mast cells following exocytic exclusion of biodegradable polymeric nanoparticles.

    Science.gov (United States)

    Tahara, Kohei; Tadokoro, Satoshi; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Hirashima, Naohide

    2012-01-01

    The objective of this study is to evaluate the effect of polymeric nanoparticles (NPs) on the allergic response of mast cells that release inflammatory mediators such as histamine through exocytosis. Submicron-sized biodegradable poly(DL-lactide-co-glycolide) (PLGA) NPs were prepared by the emulsion solvent diffusion method. Here, we examined the interactions of the mast cells with two types of PLGA NPs, unmodified NPs and NPs modified with chitosan (CS), a biodegradable cationic polymer. The cellular uptake of NPs increased by CS modification due to electrostatic interactions with the plasma membrane. NPs were taken up by mast cells through an endocytic pathway (endocytic phase) and then the cellular uptake was saturated and maintained plateau level by the exclusion of NPs through exocytosis (exocytic phase). Antigen-induced histamine release from mast cells was inhibited during the exocytic phase. The extent of histamine release inhibition was related to the amount of excluded NPs. Exocytic exclusion of NPs competitively antagonize the antigen-induced exocytotic release of histamine by highjacking exocytosis machinery such as SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, since histamine release was recovered in mast cells that overexpress SNAP-23. The inhibitory effect of the allergic response by PLGA NPs was also evaluated in vivo using the mouse model for systemic anaphylaxis. The administration of NPs suppressed the antigen-induced systemic allergic response in vivo. In conclusion, PLGA NP itself has actions to inhibit the allergic responses mediated by mast cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction.

    Science.gov (United States)

    Solèr, M; Joos, L; Bolliger, C T; Elsasser, S; Perruchoud, A P

    1994-11-01

    Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell-stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect.

  14. Cold urticaria patients exhibit normal skin levels of functional mast cells and histamine after tolerance induction

    DEFF Research Database (Denmark)

    Kring Tannert, Line; Stahl Skov, Per; Bjerremann Jensen, Louise

    2012-01-01

    Cold urticaria is a skin condition characterized by rapid appearance of itchy wheals and occasionally angioedema in response to cold stimulation. Antihistamines do not sufficiently protect all patients from symptoms, even when used in higher than standard doses. In these patients, desensitization...... to cold can be beneficial. The aim was to investigate whether desensitization can lower temperature thresholds and reduce release of histamine in the skin. Cold urticaria patients were subjected to desensitization and assessed for skin responses to cold stimulation and codeine before and after. Histamine...... prevented histamine release after skin exposure to cold. Surprisingly, skin histamine levels and release after codeine injection were found to be normal in desensitized patients....

  15. Pharmacological and functional characterisation of the wild-type and site-directed mutants of the human H1 histamine receptor stably expressed in CHO cells.

    Science.gov (United States)

    Moguilevsky, N; Varsalona, F; Guillaume, J P; Noyer, M; Gillard, M; Daliers, J; Henichart, J P; Bollen, A

    1995-01-01

    A cDNA clone for the human histamine H1 receptor was isolated from a lung cDNA library and stably expressed in CHO cells. The recombinant receptor protein present in the cell membranes, displayed the functional and binding characteristics of histamine H1 receptors. Mutation of Ser155 to Ala in the fourth transmembrane domain did not significantly change the affinity of the receptor for histamine and H1 antagonists. However, mutation of the fifth transmembrane Asn198 to Ala resulted in a dramatic decrease of the affinity for histamine binding, and for the histamine-induced polyphosphoinositides breakdown, whereas the affinity towards antagonists was not significantly modified. In addition, mutation of another fifth transmembrane amino acid, Thr194 to Ala also diminished, but to a lesser extent, the affinity for histamine. These data led us to propose a molecular model for histamine interaction with the human H1 receptor. In this model, the amide moiety of Asn198 and the hydroxyl group of Thr194 are involved in hydrogen bonding with the nitrogen atoms of the imidazole ring of histamine. Moreover, mutation of Thr194 to Ala demonstrated that this residue is responsible for the discrimination between enantiomers of cetirizine.

  16. Midbody Accumulation in Breast Cancer Cells

    Science.gov (United States)

    2009-08-01

    cancer cells undergo asymmetric events during cell division that generate different daughter cells. One daughter receives the singular midbody (MB) that is made during every cell division. The cell with this so-called postmitotic midbody derivative accumulates additional MBds with successive divisions. In breast tumor sections, rare cells stain for MBds adjacent to the basal layer, the position of putative breast cancer stem cells. MBds are present in high numbers in several human breast cancer cell lines and in human tumors, but are rarely found in normal breast

  17. Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-alpha and histamine whereas normal keratinocytes undergo cytolysis.

    Science.gov (United States)

    Diaconu, Nicolae-Costin; Rummukainen, Jaana; Mättö, Mikko; Naukkarinen, Anita; Harvima, Rauno J; Pelkonen, Jukka; Harvima, Ilkka T

    2008-02-07

    Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-alpha are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-alpha and histamine on cervical carcinoma cell lines was studied. TNF-alpha alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-alpha and histamine in combination showed no additional effect over that by TNF-alpha alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-alpha-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-alpha and histamine. In comparison, TNF-alpha or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR) I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-alpha immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes. SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-alpha and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-alpha could even enhance carcinoma cell migration.

  18. Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis

    Directory of Open Access Journals (Sweden)

    Harvima Rauno J

    2008-02-01

    Full Text Available Abstract Background Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-α are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-α and histamine on cervical carcinoma cell lines was studied. Methods and results TNF-α alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-α and histamine in combination showed no additional effect over that by TNF-α alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-α-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-α and histamine. In comparison, TNF-α or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-α immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes. Conclusion SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-α and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-α could even enhance carcinoma cell migration.

  19. Increased Na+/K(+)-pump activity and adenosine triphosphate utilization after compound 48/80-induced histamine secretion from rat mast cells

    DEFF Research Database (Denmark)

    Johansen, Torben; Praetorius, Birger Hans

    1994-01-01

    The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP) were studied in rat peritoneal mast cells after histamine secretion induced by compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive technique (86Rb+). The ATP content and the glycolytic ATP...... was the limiting factor for the activity of the Na+/K(+)-pump following histamine secretion under these conditions. It is concluded that the large increase in Na+/K(+)-pump activity after a secretory response is a likely explanation for the long lasting ATP-decrease in mast cells that follows histamine secretion....

  20. Nascent histamine induces α-synuclein and caspase-3 on human cells.

    Science.gov (United States)

    Caro-Astorga, Joaquín; Fajardo, Ignacio; Ruiz-Pérez, María Victoria; Sánchez-Jiménez, Francisca; Urdiales, José Luis

    2014-09-05

    Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein-protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Sickle erythrocytes enhance phenylephrine and histamine ...

    African Journals Online (AJOL)

    Sickle erythrocytes enhance phenylephrine and histamine contractions of isolated rabbit carotid arteries. ... enhancement of histamine contractions, compared with phenylephrine (in AS and SS), suggests a possible role for histamine in the increased vascular tone and vaso-occlusive crisis in sickle cell disease.

  2. Effects of histamine and activators of the cyclic AMP system on protein synthesis in and release of high molecular weight glycoproteins from isolated gastric non-parietal cells.

    OpenAIRE

    Heim, H. K.; Oestmann, A.; Sewing, K. F.

    1991-01-01

    1. Glycoprotein and protein synthesis in and release from pig isolated, enriched gastric mucous cells were measured by the incorporation of N-acetyl-[14C]-D-glucosamine and [3H]-L-leucine, respectively, into cellular and released acid precipitable material. 2. Histamine and activators of the adenosine 3':5'-cyclic monophosphate (cyclic AMP) system maximally stimulated total protein and glycoprotein synthesis in and release from the cells at concentrations of histamine (10 microM), forskolin (...

  3. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    Science.gov (United States)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  4. Degradation of Histamine by Lactobacillus plantarum Isolated from Miso Products.

    Science.gov (United States)

    Kung, Hsien-Feng; Lee, Yi-Chen; Huang, Ya-Ling; Huang, Yu-Ru; Su, Yi-Cheng; Tsai, Yung-Hsiang

    2017-10-01

    Histamine is a toxic chemical and is the causative agent of food poisoning. This foodborne toxin may be degraded by the oxidative deamination activity of certain microorganisms. In this study, we isolated four histamine-degrading Lactobacillus plantarum bacteria from miso products. Among them, L. plantarum D-103 exhibited 100% degradation of histamine in de Man Rogosa Sharpe (MRS) broth containing 50 ppm of histamine after 24 h of incubation at 30°C. The optimal growth, histamine oxidase, and histamine-degrading activity of L. plantarum D-103 were observed in histamine MRS broth at pH 7.0, 3% NaCl, and 30°C. It also exhibited tolerance to broad ranges of pH (4 to 10) and salt concentrations (0 to 12%) in histamine MRS broth. Therefore, the histamine-degrading L. plantarum D-103 might be used as an additive culture to prevent histamine accumulation in miso products during fermentation.

  5. Cysteinyl leukotrienes mediate histamine hypersensitivity ex vivo by increasing histamine receptor numbers

    NARCIS (Netherlands)

    Pynaert, G.; Grooten, J.; van Deventer, S. J.; Peppelenbosch, M. P.

    1999-01-01

    Hyperresponsiveness to histamine is a key feature of a variety of pathological conditions, including bronchial asthma, food allergy, colitis ulcerosa, and topical allergic disorders. Cells isolated from hyperresponsive individuals do not display exaggerated histamine responses ex vivo and thus the

  6. Influence of action of coal dust on metabolism of histamine and serotonin in the body (clinical and experimental study)

    Energy Technology Data Exchange (ETDEWEB)

    Gridneva, N.V.; Dainega, V.G.; Talakin, Yu.N.

    1982-04-01

    Because of the role assigned to the destruction of the metabolism of biogenic amines in the pathogenesis of pneumoconiosis in miners and lack of information on metabolism of histamine and serotonin in first contact with coal dust, it was considered expedient to study peculiarities of their metabolism in the development of dust-induced lung pathology. A table shows results of a clinical study of the changes in the indicators of histamine and serotonin metabolism in miners with pneumoconiosis, those with a long period of service and a healthy control group. Miners with various forms of pneumoconiosis all show a significant increase in the histamine level of blood which may be related to the development in the presence of dust-induced lung disease of autoimmune processes accompanied by the liberation of free histamine from cells. With the increase in histamine, an increase of serotonin appears in blood of diseased miners. Long exposure to dust inflow activates metabolism of serotonin. In addition to the clinical study of diseased miners, an experimental investigation was made of the content of serotonin and histamine in organs of white rats. Table 2 shows that after introduction of coal dust over 1-4 months, the accumulation of serotonin in lungs, brain, kidneys, liver, and small intestine increased and the accumulation of histamine in liver, kidneys and brain decreased. Inhalation of dust produces a greater change in content of serotonin in organs; the intratracheal introduction of dust changes content of histamine. Results of experiment confirm destruction of metabolism of histamine and serotonin by coal/rock dust which proves need to use antiserotonins to cure lung disease. High content of histamine in blood determines need for use of antihistamine preparations especially in the presence of bronchospasms caused by effect of histamine on smooth muscle of bronchi.

  7. PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells.

    Science.gov (United States)

    Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

    2017-06-01

    Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca 2+ ([Ca 2+ ] cyt ). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca 2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca 2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction. Copyright © 2017 the American Physiological Society.

  8. A novel role for antizyme inhibitor 2 as a regulator of serotonin and histamine biosynthesis and content in mouse mast cells.

    Science.gov (United States)

    Acosta-Andrade, Carlos; Lambertos, Ana; Urdiales, José L; Sánchez-Jiménez, Francisca; Peñafiel, Rafael; Fajardo, Ignacio

    2016-10-01

    Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase and polyamine uptake. Our previous studies indicated a metabolic interplay among polyamines, histamine and serotonin in mast cells, and demonstrated that polyamines are present in mast cell secretory granules, being important for histamine storage and serotonin levels. Recently, the novel antizyme inhibitor-2 (AZIN2) was proposed as a local regulator of polyamine biosynthesis in association with mast cell serotonin-containing granules. To gain insight into the role of AZIN2 in the biosynthesis and storage of serotonin and histamine, we have generated bone marrow derived mast cells (BMMCs) from both wild-type and transgenic Azin2 hypomorphic mice, and have analyzed polyamines, serotonin and histamine contents, and some elements of their metabolisms. Azin2 hypomorphic BMMCs did not show major mast cell phenotypic alterations as judged by morphology and specific mast cell proteases. However, compared to wild-type controls, these cells showed reduced spermidine and spermine levels, and diminished growth rate. Serotonin levels were also reduced, whereas histamine levels tended to increase. Accordingly, tryptophan hydroxylase-1 (TPH1; the key enzyme for serotonin biosynthesis) mRNA expression and protein levels were reduced, whereas histidine decarboxylase (the enzyme responsible for histamine biosynthesis) enzymatic activity was increased. Furthermore, microphtalmia-associated transcription factor, an element involved in the regulation of Tph1 expression, was reduced. Taken together, our results show, for the first time, an element of polyamine metabolism -AZIN2-, so far described as exclusively devoted to the control of polyamine concentrations, involved in regulating the biosynthesis and content of other amines like serotonin and histamine.

  9. Histamine H4 Receptor mediates interleukin-8 and TNF-α release in human mast cells via multiple signaling pathways.

    Science.gov (United States)

    Chen, X-F; Zhang, Z; Dou, X; Li, J-J; Zhang, W; Yu, Y-Y; Yu, B; Yu, B

    2016-01-27

    Histamine, mainly produced by mast cells, is an important inflammatory mediator in immune response. Recently Histamine H4 Receptor (H4R) was also identified in mast cells, from which pro-inflammatory cytokines and chemokines are released. However, the mechanism of how H4R mediates these cytokines and chemokines release in mast cells was still unclear. To further explore the role of H4R in the immune inflammatory response in mast cells, we tested the release of inflammatory cytokine tumor necrosis factor-α (TNF-α), chemokine interleukin-8 (IL-8) and the relevant signaling pathways activated by H4R on LAD2 cells (a human mast cell line). We found that the release of IL-8 and TNF-α were blocked by inhibitors of PI3K, ERK and Ca2+-Calcineurin-NFAT signaling pathways, while the release of these cytokines and chemokines were enhanced by the inhibitor of P38 signaling pathway. However, inhibitors of the JNK and NF-κB signaling pathways had little effect on the expression of the pro-inflammatory mediators. Moreover, activation of the H4R could induce phosphorylation of ERK, p38 and AKT in mast cells. In conclusion, we found that H4R mediates the release of inflammatory cytokine TNF-α and chemokine IL-8 in human mast cells via PI3K, Ca2+-Calcineurin-NFAT and MAPKs signaling pathways.

  10. Differential expression and signaling of the human histamine H3 receptor isoforms of 445 and 365 amino acids expressed in human neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Nieto-Alamilla, Gustavo; Escamilla-Sánchez, Juan; López-Méndez, María-Cristina; Molina-Hernández, Anayansi; Guerrero-Hernández, Agustín; Arias-Montaño, José-Antonio

    2018-04-01

    In stably-transfected human neuroblastoma SH-SY5Y cells, we have compared the effect of activating two isoforms of 445 and 365 amino acids of the human histamine H 3 receptor (hH 3 R 445 and hH 3 R 365 ) on [ 35 S]-GTPγS binding, forskolin-induced cAMP formation, depolarization-induced increase in the intracellular concentration of Ca 2+ ions ([Ca 2+ ]i) and depolarization-evoked [ 3  H]-dopamine release. Maximal specific binding (B max ) of [ 3  H]-N-methyl-histamine to cell membranes was 953 ± 204 and 555 ± 140 fmol/mg protein for SH-SY5Y-hH 3 R 445 and SH-SY5Y-hH 3 R 365 cells, respectively, with similar dissociation constants (K d , 0.86 nM and 0.81 nM). The mRNA of the hH 3 R 365 isoform was 40.9 ± 7.9% of the hH 3 R 445 isoform. No differences in receptor affinity were found for the H 3 R ligands histamine, immepip, (R)(-)-α-methylhistamine (RAMH), A-331440, clobenpropit and ciproxifan. Both the stimulation of [ 35 S]-GTPγS binding and the inhibition of forskolin-stimulated cAMP accumulation by the agonist RAMH were significantly larger in SH-SY5Y-hH 3 R 445 cells ([ 35 S]-GTPγS binding, 158.1 ± 7.5% versus 136.5 ± 3.6% for SH-SY5Y-hH 3 R 365 cells; cAMP accumulation, -74.0 ± 4.9% versus -43.5 ± 5.3%), with no significant effect on agonist potency. In contrast, there were no differences in the efficacy and potency of RAMH to inhibit [ 3  H]-dopamine release evoked by 100 mM K + (-18.9 ± 3.0% and -20.5 ± 3.3%, for SH-SY5Y-hH 3 R 445 and SH-SY5Y-hH 3 R 365 cells), or the inhibition of depolarization-induced increase in [Ca 2+ ]i (S2/S1 ratios: parental cells 0.967 ± 0.069, SH-SY5Y-hH 3 R 445 cells 0.639 ± 0.049, SH-SY5Y-hH 3 R 365 cells 0.737 ± 0.045). These results indicate that in SH-SY5Y cells, hH 3 R 445 and hH 3 R 365 isoforms regulate in a differential manner the signaling pathways triggered by receptor activation.

  11. THE ROLE OF INOSITOL 1,3,4,5-TETRAKISPHOSPHATE IN INTERNAL CA2+ MOBILIZATION FOLLOWING HISTAMINE H-1 RECEPTOR STIMULATION IN DDT1 MF-2 CELLS

    NARCIS (Netherlands)

    VANDERZEE, L; SIPMA, H; NELEMANS, A; DENHERTOG, A

    1995-01-01

    Receptor-activated formation of inositol phosphates results in mobilization of intracellular stored Ca2+ in a variety of cells, including vas deferens derived DDT1 MF-2 cells. Stimulation of the histamine H-1 receptor on these cells caused a pronounced formation of inositol 1,3,4,5-tetrakisphosphate

  12. Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and inflammatory cells in perennial allergic rhinitis.

    Science.gov (United States)

    Dinh, Q T; Cryer, A; Dinh, S; Peiser, C; Wu, S; Springer, J; Hamelmann, E; Klapp, B F; Heppt, W; Fischer, A

    2005-11-01

    Histamine receptors play an important role in the pathogenesis of nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R transcript levels have been found to be up-regulated in perennial - but not in seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R expression in complex tissues of the nasal mucosa of perennial allergic rhinitis (PAR). Ten patients with PAR and 13 non-AR subjects were recruited for the study by medical history, physical examination and laboratory screening tests. In this study, we have analysed single cells dissected from the nasal mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was analysed in different cell types such as epithelial, endothelial, mucus and inflammatory cells isolated from the nasal mucosa of PAR in comparison with non-AR subjects. H1R mRNA gene expression level was significantly increased in the nasal mucosa of PAR in comparison with non-AR (Pcomparison with non-AR whereas H1R gene expression levels in endothelial cells between both groups were not changed (P=0.23). Interestingly, inflammatory cells in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA (Pallergic airway inflammation in PAR.

  13. Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response.

    Science.gov (United States)

    Aldinucci, Alessandra; Bonechi, Elena; Manuelli, Cinzia; Nosi, Daniele; Masini, Emanuela; Passani, Maria Beatrice; Ballerini, Clara

    2016-07-08

    Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Toll-like receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFNγ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1-4 and TLRs were determined as well. Independently of actin remodeling, histamine down-regulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response*

    Science.gov (United States)

    Bonechi, Elena; Manuelli, Cinzia

    2016-01-01

    Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Toll-like receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFNγ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1–4 and TLRs were determined as well. Independently of actin remodeling, histamine down-regulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance. PMID:27226579

  15. Stromal Interaction Molecule 1 (STIM1) and Orai1 Mediate Histamine-evoked Calcium Entry and Nuclear Factor of Activated T-cells (NFAT) Signaling in Human Umbilical Vein Endothelial Cells*

    Science.gov (United States)

    Zhou, Meng-Hua; Zheng, Hongying; Si, Hongjiang; Jin, Yixin; Peng, Jasmine M.; He, Lian; Zhou, Yubin; Muñoz-Garay, Carlos; Zawieja, David C.; Kuo, Lih; Peng, Xu; Zhang, Shenyuan L.

    2014-01-01

    Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum and eliciting Ca2+ entry across the plasma membrane. Herein, we show that histamine-evoked Ca2+ entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca2+ release-activated Ca2+ (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca2+ entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca2+ influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca2+ mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation. PMID:25190815

  16. Effects of C18 Fatty Acids on Intracellular Ca(2+) Mobilization and Histamine Release in RBL-2H3 Cells.

    Science.gov (United States)

    Kim, Myung Chul; Kim, Min Gyu; Jo, Young Soo; Song, Ho Sun; Eom, Tae In; Sim, Sang Soo

    2014-06-01

    To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca(2+) mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca(2+) mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca(2+), stearic acid (100 µM) did not cause any increase of intracellular Ca(2+) mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca(2+) mobilization, but the increase was smaller than that in the presence of extracellular Ca(2+). These results suggest that C18 fatty acid-induced intracellular Ca(2+) mobilization is mainly dependent on extracellular Ca(2+) influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca(2+) mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca(2+) mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca(2+) mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca(2+) mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation.

  17. Effects of C18 Fatty Acids on Intracellular Ca2+ Mobilization and Histamine Release in RBL-2H3 Cells

    Science.gov (United States)

    Kim, Myung Chul; Kim, Min Gyu; Jo, Young Soo; Song, Ho Sun; Eom, Tae In

    2014-01-01

    To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca2+ mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca2+ mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca2+, stearic acid (100 µM) did not cause any increase of intracellular Ca2+ mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca2+ mobilization, but the increase was smaller than that in the presence of extracellular Ca2+. These results suggest that C18 fatty acid-induced intracellular Ca2+ mobilization is mainly dependent on extracellular Ca2+ influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca2+ mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca2+ mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca2+ mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca2+ mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation. PMID:24976764

  18. Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol.

    Science.gov (United States)

    Church, M K; Hiroi, J

    1987-02-01

    The ability of the anti-allergic drugs, sodium cromoglycate (SCG), lodoxamide, traxanox, RU31156 and the beta-adrenoceptor agonist salbutamol to inhibit IgE-dependent histamine and prostaglandin D2 (PGD2) release was assessed using human dispersed lung mast cells. The anti-allergic drugs were weak inhibitors of histamine release, high concentrations (100-1000 microM) producing less than 35% inhibition. Salbutamol produced 39% inhibition at 10 microM. The efficacy of both SCG and salbutamol was inversely related to the concentration of anti-IgE used for challenge and to the degree of histamine release. Rapid tachyphylaxis was observed with all anti-allergic drugs but not with salbutamol. Cross-tachyphylaxis was observed between SCG and the other anti-allergic drugs, suggesting a common mechanism of action. No cross-tachyphylaxis was observed between SCG and salbutamol. SCG was significantly (P less than 0.001) more effective in inhibiting PGD2 than it was histamine release. Preferential inhibition of PGD2 compared with histamine release was less marked (P less than 0.05) with salbutamol and not significant with the other anti-allergic drugs. Mast cells dispersed by enzymatic digestion of human lung released more histamine on immunological challenge than mechanically dispersed cells obtained by fine chopping of tissue. Enzyme treatment of mechanically dispersed cells removed this difference. Enzymatically and mechanically dispersed cells responded similarly to the inhibitory effects of SCG and salbutamol. Our results suggest that salbutamol is a more effective inhibitor of mediator release from human lung mast cells than anti-allergic drugs. However, with the low levels of mediator release achieved during an allergic reaction in man in vivo, both salbutamol and SCG are likely to be effective inhibitors of both preformed and newly generated mediators.

  19. Bisphenol A at concentrations relevant to human exposure enhances histamine and cysteinyl leukotriene release from bone marrow-derived mast cells.

    Science.gov (United States)

    O'Brien, Edmund; Dolinoy, Dana C; Mancuso, Peter

    2014-01-01

    Bisphenol A (BPA), a monomer of polycarbonate plastics and epoxide resin, acts as an endocrine-active compound and has been shown to enhance the inflammatory response to allergen challenge. Previous reports in rodents have demonstrated that perinatal BPA exposure alters airway inflammation following sensitization and challenge to ovalbumin in juvenile and adult offspring. Additionally, a high concentration of BPA has been shown to enhance mediator release in mast cell lines. This study aimed to determine if short-term BPA exposure, at levels relevant to human exposure, enhances mast cell release of histamine and cysteinyl leukotrienes (CysLTs). Primary murine bone marrow-derived mast cells (BMMC) produced from the femurs of female C57BL/6 mice were stimulated with BPA or estradiol (E2) in vitro. It was observed that both BPA and E2 increased BMMC histamine release over a range of nanomolar concentrations (1-1000 nM). The estrogen receptor (ER) antagonist ICI 182,780 partially blocked the ability of E2, but not BPA, to elevate histamine release. BPA also increased CysLT release, which was not abrogated by ER inhibition. It was also observed that the ability of BPA to enhance histamine and CysLT release was inhibited by blocking the extracellular signal-regulated kinase (ERK) pathway with U0126 or by chelating extracellular calcium (Ca(2+)) using EGTA. In summary, these experiments are the first to demonstrate that acute BPA exposure enhances mast cell histamine and CysLT release in vitro--an effect that is not dependent on an ER-mediated mechanism. Instead, BPA-induced mast cell histamine and CysLT release may be mediated, in part, by the ERK pathway and extracellular Ca(2+) concentrations. These data suggest that exposure to BPA at levels relevant to human exposure may provoke an acute inflammatory response in atopic individuals via enhanced mast cell activation.

  20. Evidence of NK1 and NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line

    Science.gov (United States)

    1992-01-01

    and NK2 tachykinin receptors and their involvement in histamine release in a murine mast cell line 61102A 3M161 102BSI AA 6. AUTHOR(S) Krumins, SA...NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line S. A. KRUMINS and C. A. BROOMFIELD Biochemical...the biological effects of SPt, NKA and[ NKII t),ue rmeecd 28 Nla t991 are mediated through their respective tachykinin I),lie cccPIC(I3 Ociotc 1991

  1. Effects of benzalkonium chloride on histamine H1 receptor mRNA expression in nasal epithelial cells.

    Science.gov (United States)

    Kawabata, Masaki; Ohori, Junichiro; Kurono, Yuichi

    2016-12-01

    To better understand the causes of the exacerbation of rhinitis medicamentosa (RM) induced by oxymetazoline (OMZ) or benzalkonium chloride (BKC), we examined the impact of pretreatment with OMZ or BKC on cultured human nasal epithelial cells. We also examined the effect of mometasone furoate (MF) on the cultured human nasal epithelial cells treated with OMZ or BKC. Cells of the human nasal epithelial cell line HNEpC were treated with OMZ or BKC, and the OMZ- and BKC-induced expression of histamine H1 receptor (H1R) mRNA was assayed using real-time polymerase chain reaction. In some experiments, 1.0×10(-5)M MF was added to the HNEpC cells for 24h before treatment with OMZ or BKC. Treatment with OMZ slightly increased the expression level of H1R mRNA in HNEpC cells. This enhanced expression was not significantly reduced by pretreatment with MF. In contrast, treatment with BKC remarkably increased the expression level of H1R mRNA in HNEpC cells. In addition, this enhanced expression was significantly reduced by pretreatment with MF. These results suggest that the increased expression of H1R mRNA due to treatment with OMZ or BKC might be one of the factors underlying the exacerbation of symptoms in patients with RM and those complicated with allergic rhinitis. The concomitant use of a nasal steroid might reduce the exacerbation of symptoms caused by BKC, although there remains a risk of developing histamine hypersensitivity from the long-term use of a topical steroid-containing BKC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Gut Microbe-Mediated Suppression of Inflammation-Associated Colon Carcinogenesis by Luminal Histamine Production.

    Science.gov (United States)

    Gao, Chunxu; Ganesh, Bhanu Priya; Shi, Zhongcheng; Shah, Rajesh Rasik; Fultz, Robert; Major, Angela; Venable, Susan; Lugo, Monica; Hoch, Kathleen; Chen, Xiaowei; Haag, Anthony; Wang, Timothy C; Versalovic, James

    2017-10-01

    Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b + Gr-1 + immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc + Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc -/- mice. This histamine-producing probiotic decreased the number and size of colon tumors and colonic uptake of [ 18 F]-fluorodeoxyglucose by positron emission tomography in Hdc -/- mice. Administration of L. reuteri suppressed keratinocyte chemoattractant (KC), Il22, Il6, Tnf, and IL1α gene expression in the colonic mucosa and reduced the amounts of proinflammatory, cancer-associated cytokines, keratinocyte chemoattractant, IL-22, and IL-6, in plasma. Histamine-generating L. reuteri also decreased the relative numbers of splenic CD11b + Gr-1 + immature myeloid cells. Furthermore, an isogenic HDC-deficient L. reuteri mutant that was unable to generate histamine did not suppress carcinogenesis, indicating a significant role of the cometabolite, histamine, in suppression of chronic intestinal inflammation and colorectal tumorigenesis. These findings link luminal conversion of amino acids to biogenic amines by gut microbes and probiotic-mediated suppression of colorectal neoplasia. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation

    Directory of Open Access Journals (Sweden)

    Xiang Fei

    2017-05-01

    Full Text Available Gallic acid (3,4,5-trihydroxybenzoic acid, is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing (S-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several (S- and (R-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

  4. Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Jacobsen, S.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    ]arachidonic acid was converted to [C]prostaglandin D. A potentiated effect was found between thapsigargin and 12--tetradecanoylphorbol 13-acetate, as well as between A23187 and the phorbol ester with respect to release of [C]arachidonic acid and histamine. It is suggested that the synergistic effect is due......Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C...

  5. The Effects of a Chactoid Scorpion Venom and Its Purified Toxins on Rat Blood Pressure and Mast Cells Histamine Release

    Directory of Open Access Journals (Sweden)

    Philip Lazarovici

    2013-07-01

    Full Text Available The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A2 produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A2, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation.

  6. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus.

    Science.gov (United States)

    Dunford, Paul J; Williams, Kacy N; Desai, Pragnya J; Karlsson, Lars; McQueen, Daniel; Thurmond, Robin L

    2007-01-01

    Histamine is a potent mediator of itch in humans, yet histamine H(1) receptor antagonists have been shown to be of limited use in the treatment of certain chronic pruritic diseases. The histamine H(4) receptor is a recently described histamine receptor, expressed on hematopoietic cells, linked to the pathology of allergy and asthma. The contribution of the novel histamine H(4) receptor to histaminergic and allergic pruritus was investigated. Histamine and a selective histamine H(4) receptor agonist caused scratching responses in mice, which were almost completely attenuated in histamine H(4) receptor knockout mice or by pretreatment with the selective histamine H(4) receptor antagonist, JNJ 7777120. Pruritus induced by allergic mechanisms was also potently inhibited with histamine H(4) receptor antagonist treatment or in histamine H(4) receptor knockout mice. In all cases, the inhibitory effect of histamine H(4) receptor antagonist was greater than those observed with histamine H(1) receptor antagonists. The histamine H(4) receptor-mediated pruritus was shown to be independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons. These results demonstrate that the histamine H(4) receptor is involved in pruritic responses in mice to a greater extent than the histamine H(1) receptor. Histamine H(4) receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H(1) receptor antagonists are not effective.

  7. Ca2+-dependent down-regulation of human histamine H1receptors in Chinese hamster ovary cells.

    Science.gov (United States)

    Hishinuma, Shigeru; Komazaki, Hiroshi; Tsukamoto, Hayato; Hatahara, Hirokazu; Fukui, Hiroyuki; Shoji, Masaru

    2018-01-01

    G q/11 protein-coupled human histamine H 1 receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca 2+ concentrations induced by a receptor-bypassed stimulation with ionomycin, a Ca 2+ ionophore, on the endocytosis and down-regulation of H 1 receptors in Chinese hamster ovary cells. All cellular and cell-surface H 1 receptors were detected by the binding of [ 3 H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H 1 receptor ligands, mepyramine and pirdonium, respectively. The pretreatment of cells with ionomycin markedly reduced the mepyramine- and pirdonium-sensitive binding sites of [ 3 H]mepyramine, which were completely abrogated by the deprivation of extracellular Ca 2+ and partially by a ubiquitin-activating enzyme inhibitor (UBEI-41), but were not affected by inhibitors of calmodulin (W-7 or calmidazolium) and protein kinase C (chelerythrine or GF109203X). These ionomycin-induced changes were also not affected by inhibitors of receptor endocytosis via clathrin (hypertonic sucrose) and caveolae/lipid rafts (filipin or nystatin) or by inhibitors of lysosomes (E-64, leupeptin, chloroquine, or NH 4 Cl), proteasomes (lactacystin or MG-132), and a Ca 2+ -dependent non-lysosomal cysteine protease (calpain) (MDL28170). Since H 1 receptors were normally detected by confocal immunofluorescence microscopy with an antibody against H 1 receptors, even after the ionomycin treatment, H 1 receptors appeared to exist in a form to which [ 3 H]mepyramine was unable to bind. These results suggest that H 1 receptors are apparently down-regulated by a sustained increase in intracellular Ca 2+ concentrations with no process of endocytosis and lysosomal/proteasomal degradation of receptors. © 2017 International Society for Neurochemistry.

  8. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    Science.gov (United States)

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells.

    Science.gov (United States)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100μM) and doxorubicin (0.2µM) decreased the cell survival rate, but olanzapine (1-100µM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. Copyright © 2016 Elsevier Inc

  10. Stimulatory effects of histamine on migration of nasal fibroblasts.

    Science.gov (United States)

    Hong, Sung-Moon; Park, Il-Ho; Um, Ji-Young; Shin, Jae-Min; Lee, Heung-Man

    2015-10-01

    Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts. Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Cells were treated with histamine and/or histamine receptor-selective antagonists. U-73122 and pertussis toxin, which are selective inhibitors of the lower signaling pathway of H1R and H4R, were used to confirm the modulation of nasal fibroblast migration by histamine. Fibroblast cytoskeletal structures were visualized with immunocytochemistry. Histamine significantly stimulated the migration of nasal fibroblasts. Antagonists selective for HR1 and HR4 significantly reduced nasal fibroblast migration. In immunocytochemical staining, histamine treatment increased membrane ruffling and pyrilamine, diphenhydramine, fexofenadine, and JNJ7777120 decreased histamine-induced membrane ruffling. U-73122 and pertussis toxin also decreased histamine-induced migration of fibroblasts. Histamine maintains its stimulatory effects on fibroblast migration in the presence of mitomycin C, which blocks proliferation of cells. We showed that histamine stimulates fibroblast migration in nasal fibroblasts. This effect appeared to be mediated by HR1 and HR4. However, because fibroblast migration also can be involved in scaring and fibrosis, more research is necessary to determine the effects of antihistamine on wound healing after sinus surgery. © 2015 ARS-AAOA, LLC.

  11. The study of accumulation of Sr 90 by plant cells

    International Nuclear Information System (INIS)

    Matusov, G.D.; Kudryashova, N.N.

    2002-01-01

    In this work the absorption and desorption of ions Sr 90 by plant cells and influence of different physical and chemical factors of environment on that processes were investigated. The kinetics of strontium accumulation have been obtained and the factors of accumulation of Sr 90 have been determined for a plant cell itself and its separate compartments

  12. Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors

    OpenAIRE

    1991-01-01

    Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after...

  13. Neomycin inhibits histamine and thapsigargin mediated Ca2+ DDT1 MF-2 cells independent of phospholipase C activation

    NARCIS (Netherlands)

    Sipma, H; VanderZee, L; DenHertog, A; Nelemans, A

    1996-01-01

    The histamine H-1 receptor mediated increase in cytoplasmic Ca2+ ([Ca2+](i)) was measured in the presence of the known phospholipase C (PLC) inhibitor, neomycin. Neomycin (1 mM) inhibited the histamine (100 mu M) induced rise in [Ca2+](i) to the same extent as observed after blocking Ca2+ entry with

  14. Modulation of human dermal microvascular endothelial cells by Sarcoptes scabiei in combination with proinflammatory cytokines, histamine, and lipid-derived biologic mediators

    Science.gov (United States)

    Elder, B. Laurel; Arlian, Larry G.; Morgan, Marjorie S.

    2009-01-01

    The ectoparasitic mite, Sarcoptes scabiei, produces molecules that depress initiation of host inflammatory and immune responses. Some of these down-regulate expression of adhesion molecules or secretion of chemokines or cytokines on and by cultured dermal endothelial cells (HMVEC-D). This study was undertaken to determine if the response of HMVEC-D to scabies is altered in the presence of various proinflammatory cytokines (tumor necrosis factor α and interleukins 1α, 1β and 6), histamine, and lipid-derived mediators (prostaglandins D2 and E2, leukotriene B4, platelet activation factor) that likely occur in scabietic lesions in vivo. Scabies extract down-regulated the TNFα-induced expression of VCAM-1 by HMVEC-D and this down-regulation still occurred in the presence of the other proinflammatory cytokines, histamine or the lipid-derived mediators. Scabies inhibited the IL-1α and IL-1β-induced secretion of IL-6, while a combination of scabies and histamine or LTB4 reduced the TNFα-induced secretion of IL-6. Scabies extract inhibited secretion of IL-8. Histamine, PGD2, PGE2, LTB4, PAF, and IL-6 alone had no effect on this inhibition, but the scabies-induced inhibition of IL-8 secretion was reduced in a dose-dependent fashion in the presence of IL-1α and IL-1β. PMID:19523846

  15. Persistent Histamine Excitation of Glutamatergic Preoptic Neurons

    Science.gov (United States)

    Tabarean, Iustin V.

    2012-01-01

    Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca2+ concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons. PMID:23082195

  16. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  17. Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells.

    Science.gov (United States)

    Stegajev, Vasili; Kouri, Vesa-Petteri; Salem, Abdelhakim; Rozov, Stanislav; Stark, Holger; Nordström, Dan C E; Konttinen, Yrjö T

    2014-12-01

    Apoptosis is involved in the pathogenesis of Sjögren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H₄R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H₄R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H₄R agonist HST-10. Expression and internalization of H₄R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H₄R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H₄R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H₄R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H₄R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H₄R activation on apoptosis of human salivary gland cells. Diminished H₄R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular.

  18. Structure-activity relationship of a series of 17 parabens and related compounds for histamine release in rat peritoneal mast cells and skin allergic reaction in guinea pigs.

    Science.gov (United States)

    Uramaru, Naoto; Inoue, Toshio; Watanabe, Yoko; Shigematsu, Hidenari; Ohta, Shigeru; Kitamura, Shigeyuki

    2014-02-01

    Parabens, which are a homologous series of esters of p-hydroxybenzoic acid, have been used as preservatives in cosmetics, medicines and foods because of their antimicrobial activity. However, parabens in cosmetics have been suspected to cause allergic contact dermatitis. In this study, we examined paraben-induced histamine release from rat peritoneal mast cells and skin reaction in guinea pigs using a series of 17 parabens with different alcohol side chains, ranging from methylparaben to dodecylparaben. Octylparaben showed the greatest histamine release-inducing activity from mast cells, and the activity was decreased in shorter- and longer-side-chain parabens. Octyl benzoate, octyl o-hydroxybenzoate and phenyloctane caused no significant degranulation of mast cells, whereas octyl m-hydroxybenzoate, octyl p-hydroxybenzoate and octyl phenol induced concentration-related degranulation. Metabolites of these parabens (p-hydroxybenzoic acid and alcohols) did not show histamine release-inducing activity. In the guinea pig skin reaction test, heptylparaben induced a typical strong skin reaction, while butylparaben induced a typical weak skin reaction, and methylparaben and dodecylparaben were inactive. Metabolites of parabens (p-hydroxybenzoic acid and alcohols) were also inactive. These results indicate that interaction of parabens with rat mast cells requires a minimum length and adequate lipophilicity of the alkyl side chain. Since metabolites of parabens were inactive, parabens appear to be direct-acting allergens.

  19. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

    1996-01-01

    Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during...... storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine...... content at donation, and histamine concentration in samples drawn from the units on days 0, 2, 5, 9, 14, 21, 28 and 35 were analysed with an enzyme-linked immunosorbent assay. Median plasma histamine concentration was 4.8 (range 1.9-14.3) nmol/l (n = 18). Median total cell-bound histamine content was 417...

  20. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

    1996-01-01

    storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine...... content at donation, and histamine concentration in samples drawn from the units on days 0, 2, 5, 9, 14, 21, 28 and 35 were analysed with an enzyme-linked immunosorbent assay. Median plasma histamine concentration was 4.8 (range 1.9-14.3) nmol/l (n = 18). Median total cell-bound histamine content was 417......Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during...

  1. Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation

    OpenAIRE

    Chang, Yung-Lung; Lin, Chun-Shu; Wang, Hsing-Won; Jian, Kai Ren; Liu, Shao-Cheng

    2017-01-01

    Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress. Objective: This study sought to determine the effects of histamine and chlorpheniramine on AQP5 expression in human nasal epithelial cells (HNEpC) and to detect the signaling cascades responsible for these effects. Methods: HNEpC were cultured with four concentrations of h...

  2. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies

    OpenAIRE

    Wood, J D

    2006-01-01

    There is altered expression of histamine H1 and H2 receptor subtypes in mucosal biopsies from the terminal ileum and large intestine of patients with symptoms of food allergy and/or irritable bowel syndrome

  3. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H₁ and H₂ receptors in vitro.

    Science.gov (United States)

    Zhang, Luyi; Yao, Ke; Fan, Yanying; He, Ping; Wang, Xiaofen; Hu, Weiwei; Chen, Zhong

    2012-12-01

    Although it is believed that carnosine has protective effects on various cell types, its effect on microvascular endothelial cells has not been well defined. In the present study, we investigated the protective effects of carnosine in microvascular endothelial cells using an in vitro rotenone-induced oxidative stress model. Mouse brain microvascular endothelial cells were exposed to 1 μmol/L rotenone for 18 h. In some experiments, carnosine (100 nmol/L-1 mmol/L) was added 30 min prior to rotenone exposure. When used, histamine receptor antagonists (100 nmol/L-10 μmol/L) were added 15 min before carnosine treatment. After rotenone exposure, apoptosis of microvascular cells was analysed by Hoechst 33342 staining, whereas mitochondrial membrane potential was assessed by JC-1 staining. Intracellular carnosine and histamine levels were determined using HPLC or ultra-HPLC. Over the range 1 μmol/L-1 mmol/L, carnosine concentration-dependently decreased the number of apoptotic cells after 18 h exposure to rotenone. This effect was reversed by the histamine H1 receptor antagonists pyrilamine and diphenhydramine (1 and 10 μmol/L) and the H2 receptor antagonists cimetidine (100 nmol/L-10 μmol/L) and zolatidine (10 μmol/L). α-Fluoromethylhistidine (100 μmol/L), a selective and irreversible inhibitor of histidine decarboxylase, also significantly inhibited the protective effects of carnosine. At 0.1 mmol/L, carnosine restored the decrease in mitochondrial membrane potential after 6 h exposure to 1 μmol/L rotenone and this effect was also reversed by the H1 and H2 receptor antagonists. Moreover, intracellular carnosine levels increased as early as 1 h after carnosine treatment, whereas intracellular histamine levels increased 18 h after carnosine treatment. The results of the present study indicate that carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury via histamine H1 and H2 receptors. The

  4. Inhibition of gastric acid secretion by epidermal growth factor. Effects on cyclic AMP and on prostaglandin production in rat isolated parietal cells.

    OpenAIRE

    Hatt, J F; Hanson, P J

    1988-01-01

    Histamine (0.5 mM) stimulated the cyclic AMP content of cell suspensions containing greater than 80% parietal cells. Epidermal growth factor (EGF) inhibited this stimulatory effect of histamine, but had no effect on basal cyclic AMP content. The half-maximally effective concentration of EGF for inhibition of histamine-stimulated cyclic AMP was 3.9 nM. The equivalent measurement for the inhibition of histamine-stimulated aminopyrine accumulation was 3.0 nM. Aminopyrine accumulation was measure...

  5. Cadmium impact, accumulation and detection in poplar callus cells.

    Science.gov (United States)

    Kollárová, Karin; Vatehová, Zuzana; Kučerová, Danica; Lišková, Desana

    2017-06-01

    Effect of cadmium cations and their interaction with silicon cations was determined in poplar calli and expressed as changes in callus growth, cell viability and cadmium cation accumulation. Cell viability throughout culture versus cadmium cation accumulation in cells is discussed. At the same time, the study sought appropriate methods for cadmium cation detection in callus cells and also in experiments with low plant material (e.g. protoplasts). Cadmium cations were determined by atomic absorption spectroscopy and using fluorescence microscopy with a specific cadmium cation fluorescent dye. The detection of cadmium cations in callus cells by the latter method appears suitable because the callus cells are surrounded by primary cell walls without auto-fluorescence and these values fit well with atomic absorption spectroscopy quantification. However, the visualisation method has some limits discussed below.

  6. Cytopathology and exocrine dysfunction induced in ex vivo rabbit lacrimal gland acinar cell models by chronic exposure to histamine or serotonin.

    Science.gov (United States)

    McDonald, Michelle L; Wang, Yanru; Selvam, Shivaram; Nakamura, Tamako; Chow, Robert H; Schechter, Joel E; Yiu, Samuel C; Mircheff, Austin K

    2009-07-01

    Lacrimal immunohistopathology has diverse clinical presentations, suggesting that inflammatory mediators exert diverse influences. Chronic exposure to agonistic acetylcholine receptor autoantibodies has been studied previously; the present work addressed mediators that signal through other G protein-coupled receptors. Acinus-like structures and reconstituted acinar epithelial monolayers from rabbit lacrimal glands were exposed to varying concentrations of histamine or 5-hydroxytryptamine (5-HT) for 20 hours. Net and vectorial beta-hexosaminidase secretion, cytosolic Ca(2+) (Ca(i)) elevation, apical recruitment of p150(Glued), actin microfilament meshwork organization, and ultrastructure were assessed. Histamine and 5-HT acutely stimulated beta-hexosaminidase secretion at lower, but not higher, concentrations. Neither of them acutely elevated Ca(i) levels. Both recruited p150(Glued) at concentrations that failed to induce secretion. Chronic exposure to 10 mM histamine inhibited carbachol (CCh)-induced beta-hexosaminidase secretion and prevented the formation of continuous monolayers; 1 mM 5-HT partially inhibited secretion at the apical medium. Neither altered secretion to the basal medium. Chronic exposure to histamine or 5-HT partially decreased CCh induced Ca(i) elevations and p150(Glued) recruitment, even at concentrations that did not inhibit secretion. Both expanded acinar lumina and thickened microfilament meshworks, and both caused homotypic fusion of secretory vesicles and formation of aqueous vacuoles in the apical and basal cytoplasm. Chronic exposure to forskolin, which activates adenylyl cyclase, induced similar cytopathologic changes but impaired secretion modestly and only at the highest concentration tested. Inflammatory mediators that signal through G protein-coupled receptors cause acinar cell cytopathology and dose-dependent reductions of CCh-induced beta-hexosaminidase secretion. Although agonistic acetylcholine receptor autoantibodies may cause

  7. Histamine and histamine type-2 receptor antagonists in psoriasis. Mechanisms and speculations

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1991-01-01

    The findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raise the possibility that cellular immune processes may play a major role in the pathogenesis of this disease. It is broadly agreed that histamine released by mast cells is one of the molecules involved...... in the pathogenesis. This is supported by the findings that CsA and methotrexate (Mxt) reduce formation and release of histamine. However, the well known side-effects of CsA and Mxt may argue potential use of other agents acting on formation and action of histamine. Such agents may be the histamine-2 receptor...... antagonists, previously reported to have a clinical effect on psoriasis. But randomised short-term studies have disclosed that these drugs have no beneficial or even an aggravating effect on the disease. This article reports on recent findings of improvement in psoriasis using high doses of the histamine-2...

  8. Histamine induces NF-κB controlled cytokine secretion by orbital fibroblasts via histamine receptor type-1

    NARCIS (Netherlands)

    S. Virakul (Sita); T. Phetsuksiri (Tanachaporn); C. van Holten-Neelen; B. Schrijver (Benjamin); L. van Steensel (Leendert); V.A.S.H. Dalm (Virgil); A.D.A. Paridaens (Dion); W.A. van den Bosch (Willem); P.M. van Hagen (Martin); W.A. Dik (Willem)

    2016-01-01

    textabstractMast cells and their products are likely to be involved in regulating orbital fibroblast activity in Graves' Ophthalmopathy (GO). Histamine is abundantly present in granules of mast cells and is released upon mast cell activation. However, the effect of histamine on orbital fibroblasts

  9. In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

    Science.gov (United States)

    Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

    2016-04-15

    It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Role of Histamine and Its Receptors in Cerebral Ischemia

    Science.gov (United States)

    2012-01-01

    Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application. PMID:22860191

  11. Effect of sodium butyrate treatment on the granule morphology, histamine level and elemental content of the bone marrow-derived mast cell

    International Nuclear Information System (INIS)

    Rydzynski, K.; Dalen, H.

    1994-01-01

    Mast cells derived from the bone marrow of BALB/c mice (BMMC) were cultures and their growth ceased with sodium butyrate. Sodium butyrate treatment (1 mM, 4 days) caused maturation of the granules, and increased histamine content from approx. 1 pg/cell to 4 pg/cell. X-ray microanalysis revealed that maturation of the granules was accompanied by the increase in relative weight percent of sodium, phosphorus and sulphur, with concomitant decrease in chloride. The sulphur to potassium ratio increased three-fold in butyrate-treated mast cells. The existence of a different elemental composition during mast cell maturation may provide additional parameter for rapid discrimination of mast cell subpopulations. (author). 28 refs, 6 figs

  12. Histamine and the striatum.

    Science.gov (United States)

    Bolam, J Paul; Ellender, Tommas J

    2016-07-01

    The neuromodulator histamine is released throughout the brain during periods of wakefulness. Combined with an abundant expression of histamine receptors, this suggests potential widespread histaminergic control of neural circuit activity. However, the effect of histamine on many of these circuits is unknown. In this review we will discuss recent evidence for histaminergic modulation of the basal ganglia circuitry, and specifically its main input nucleus; the striatum. Furthermore, we will discuss recent findings of histaminergic dysfunction in several basal ganglia disorders, including in Parkinson's disease and most prominently, in Tourette's syndrome, which has led to a resurgence of interest in this neuromodulator. Combined, these recent observations not only suggest a central role for histamine in modulating basal ganglia activity and behaviour, but also as a possible target in treating basal ganglia disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Activation of the Na+/K(+)-pump in rat peritoneal mast cells following histamine release: a possible role in cell recovery

    DEFF Research Database (Denmark)

    Knudsen, T; Ferjan, I; Johansen, Torben

    1993-01-01

    1. The activity of the Na+/K(+)-pump in rat peritoneal mast cells was measured at various time intervals after induction of cellular histamine release by compound 48/80 or by the antigen-antibody reaction. The Na+/K(+)-pump activity was assessed as the ouabain-sensitive potassium uptake...... of the cells using 86Rb+ as a tracer for potassium (K+(86Rb+)-uptake). 2. Stimulation of the cells with compound 48/80 induced a time and concentration dependent increase of the Na+/K(+)-pump activity. The pump activity was maximal 2 min after stimulation of the cells. Then, the activity gradually decreased...... and reached a level not significantly different from the controls after 2 h of incubation. 3. When the cells were stimulated by the antigen-antibody reaction, there was also a rapid (within 5 min) stimulation of the Na+/K(+)-pump. In contrast to the stimulation with compound 48/80, the pump activity returned...

  14. 3H-histamine release from human leukocytes

    International Nuclear Information System (INIS)

    Stahl Skov, P.; Norn, S.; Weeke, B.

    1979-01-01

    A rapid, simple, and inexpensive method for large scale screening of patients suspected of type I allergy has been developed. The method is based on in vitro incorporation of 3 H-histamine in the leukocytes of the patient, whereafter release of labelled histamine is measured after provocation of the cells with the suspected allergen. The new method was compared with the conventional basophil histamine release technique by in vitro provocation of six asthmatic patients under suspicion of type I allergy against animal dander, house dust, and mite, and an almost identical release of histamine was observed in both assays. (author)

  15. Histamine induces human lung fibroblast-mediated collagen gel contraction via histamine H1 receptor.

    Science.gov (United States)

    Horie, Masafumi; Saito, Akira; Yamauchi, Yasuhiro; Mikami, Yu; Sakamoto, Makiko; Jo, Taisuke; Nakajima, Jun; Takizawa, Hajime; Nagase, Takahide; Kohyama, Tadashi

    2014-06-01

    Airway remodeling is implicated in irreversible airflow limitation of refractory asthma, which includes increased smooth muscle mass and subepithelial fibrosis. Activated fibroblasts acquire contractile phenotype to participate in tissue contraction and structural alteration of extracellular matrices. Histamine is a potent mediator of allergic inflammation, substantially involved in asthmatic pathophysiology. We hypothesized that histamine might play a role in airway remodeling, and investigated its effect on fibroblast-mediated collagen gel contraction. Fibroblast-mediated collagen gel contraction was studied. Histamine's regulation of collagen gel contraction was characterized by using specific histamine-receptor antagonists, an IP3 receptor antagonist and a PKC inhibitor. Histamine induced contraction of collagen gels embedded with human lung fibroblasts, in a time-dependent manner, and at the concentration more than 10(-6) M, both in four primary cultured adult lung fibroblasts and three fetal lung fibroblast cell lines. This effect was attenuated by H1 receptor antagonist, whereas those for H2 to H4 receptors failed to show an inhibitory effect. Furthermore, IP3 receptor-mediated Ca(2+) mobilization was implicated in histamine's action on collagen gel contraction. Our results suggest that histamine is involved in airway remodeling through its action on lung fibroblasts, and antihistamine drugs, especially H1 receptor antagonists, might be potentially beneficial for a subset of asthmatic patients.

  16. C-terminal of human histamine H1receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

    Science.gov (United States)

    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

  17. The neglected role of histamine in Alzheimer's disease.

    Science.gov (United States)

    Naddafi, Fatemeh; Mirshafiey, Abbas

    2013-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques accumulation and cognitive impairment. Both environmental factors and heritable predisposition have a role in AD. Histamine is a biogenic monoamine that plays a role in several physiological functions, including induction of inflammatory reactions, wound healing, and regeneration. The Histamine mediates its functions via its 4 G-protein-coupled Histamine H1 receptor (H1R) to histamine H1 receptor (H4R). The histaminergic system has a role in the treatment of brain disorders by the development of histamine receptor agonists, antagonists. The H1R and H4R are responsible for allergic inflammation. But recent studies show that histamine antagonists against H3R and regulation of H2R can be more efficient in AD therapy. In this review, we focus on the role of histamine and its receptors in the treatment of AD, and we hope that histamine could be an effective therapeutic factor in the treatment of AD.

  18. Activation of the canonical beta-catenin pathway by histamine

    NARCIS (Netherlands)

    Diks, Sander H.; Hardwick, James C.; Diab, Remco M.; van Santen, Marije M.; Versteeg, Henri H.; van Deventer, Sander J. H.; Richel, Dick J.; Peppelenbosch, Maikel P.

    2003-01-01

    Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/beta-catenin-responsive construct in HeLa

  19. New approach for the diagnosis of histamine intolerance based on the determination of histamine and methylhistamine in urine.

    Science.gov (United States)

    Comas-Basté, Oriol; Latorre-Moratalla, M Luz; Bernacchia, Roberta; Veciana-Nogués, M Teresa; Vidal-Carou, M Carmen

    2017-10-25

    Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by diamine oxidase (DAO) enzyme deficiency, which provokes its accumulation in plasma and the appearance of adverse health affects. A new approach for the diagnosis of this intolerance could be the determination of histamine and its metabolites in urine. The aim of this work was to develop and validate a rapid method to determine histamine and methylhistamine in human urine by Ultra High Performance Liquid Chromatography and Fluorimetric detection (UHPLC-FL). The proposed method is a consistent procedure to determine histamine and methylhistamine in less than 11min with adequate linearity and sensitivity. Relative standard deviation was always lower than 5.5%, ensuring method precision; and mean recovery was greater than 99% for both analytes. The structure of histamine and methylhistamine conjugated with OPA were confirmed by UHPLC-ITD-FTMS which enabled to unequivocally identify both analytes in standards and also in urine samples. The analysis of histamine and methylhistamine in urine samples could be a potential new approach for the routine diagnosis of histamine intolerance, more patient-friendly and with clear advantages in terms of equipment and personnel demand for sample collection in comparison with current plasmatic DAO activity determination. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. On histamine and appetites

    Directory of Open Access Journals (Sweden)

    Fernando eTorrealba

    2012-07-01

    Full Text Available Brain histamine may influence a variety of different behavioral and physiological functions, but its responsibility in waking up has casted a long shadow on other important functions of this neurotransmitter. Here we review evidence indicating a central role of brain histamine in motivation, emphasizing its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control the histaminergic neurons of the tuberomamillary nucleus of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles and in food anticipatory activity. We review evidence supporting a dysfunction of histamine neurons and its cortical input in certain forms of decreased motivation (apathy. We finally discuss the relationship between the histamine system and drug addiction as a dysfunction of motivation.

  1. Copper accumulation in COMMD1-knockdown mouse hepatoma cells

    International Nuclear Information System (INIS)

    Miyayama, T.; Ogra, Y.; Hiraoka, D.; Kawaji, F.; Nakamura, E.; Suzuki, N.; Suzuki, K.T.

    2009-01-01

    Complete text of publication follows. It is suggested that mammalian cells strictly regulate copper (Cu) homeostasis. However, the Cu regulation is not fully understood. Cu metabolism domain containing 1 (COMMD1) is a protein which is associated with copper homeostasis in cells. To clarify the function of COMMD1 in Cu excretion, mouse hepatoma cells, Hepa 1-6, targeted on the COMMD1 gene were analyzed by multi-disciplinal techniques consisting of elemental imaging and speciation in addition to molecular and cellular biological techniques. COMMD1 knockdown inhibited the Cu excretion resulting in the Cu accumulation, and Cu accumulating in the cells predominantly existed in the form bound to metallothionein (MT). It is known that Atp7b, an ATP-dependent Cu transporter in the liver, localizes on trans Golgi membrane under basal Cu condition and translocates to cytoplasmic vesicles to excrete Cu when Cu concentration exceeds a certain threshold, and the vesicles disperse in the periphery of the cell. COMMD1 knockdown abolished the relocation of Atp7b from the periphery to the trans Golgi membrane when Cu concentration was returned to normal physiological level on treatment with a Cu (I) chelator. These results suggest that COMMD1 facilitates recruitment of Atp7b from cytoplasmic vesicles to trans Golgi membrane, i.e., COMMD1 is required to shuttle Atp7b when the intracellular Cu level returns to normal physiological level.

  2. Histamine type I (H1) receptor radioligand binding studies on normal T cell subsets, B cells, and monocytes

    International Nuclear Information System (INIS)

    Cameron, W.; Doyle, K.; Rocklin, R.E.

    1986-01-01

    A single, specific binding site for [ 3 H]pyrilamine on normal human T helper, T suppressor, B cells, and monocytes was documented. The binding of the radioligand to its receptor is reversible with cold H 1 antagonist, saturates at 40 to 60 nM, and binding equilibrium is achieved in 2 to 4 min. Using a computer program (Ligand), the authors calculated the dissociation constants, binding capacities, and numbers of receptors per cell for each of the different cell types. Monocytes were found to have the highest affinity for [ 3 H]pyrilamine, followed by T helper cells, B cells and T suppressor cells (K/sub D/ = 44.6 +/- 49.4 nM). T suppressor cells were found to express the higher number of H 1 receptors per cell followed by B cells, T helper cells, and monocytes. The binding affinity for [ 3 H]pyrilamine increased over a 48-hr period, whereas the number of receptors per T cell was essentially unchanged. In contrast, T cells stimulated with Con A or PHA were shown to have a greater than fourfold increase in the number of receptors per cell, whereas the binding affinity for [ 3 H]pyrilamine decreased over the 48-hr period. Although the function of H 1 receptors on T cells, B cells, and monocytes has not been completely defined, this receptor has the potential of playing an important role in the modulating the immune response

  3. Characterization of a novel bacteriophage, Phda1, infecting the histamine-producing Photobacterium damselae subsp. damselae.

    Science.gov (United States)

    Yamaki, S; Kawai, Y; Yamazaki, K

    2015-06-01

    Photobacterium damselae subsp. damselae is a potent histamine-producing micro-organism. The aim of this study was to isolate and characterize a bacteriophage Phda1 that infected P. damselae subsp. damselae to inhibit its growth and histamine accumulation. Phda1 was isolated from a raw oyster, and the host range, morphology and the bacteriophage genome size were analysed. Phda1 formed a clear plaque only against P. damselae subsp. damselae JCM8969 among five Gram-positive and 32 Gram-negative bacterial strains tested. Phda1 belongs to the family Myoviridae, and its genome size was estimated as 35·2-39·5 kb. According to the one-step growth curve analysis, the latent period, rise period and burst size of Phda1 were 60 min, 50 min and 19 plaque-forming units per infected cell, respectively. Divalent cations, especially Ca(2+) and Mg(2+) , strongly improved Phda1 adsorption to the host cells and its propagation. Phda1 treatment delayed the growth and histamine production of P. damselae subsp. damselae in an in vitro challenge test. The bacteriophage Phda1 might serve as a potential antimicrobial agent to inhibit the histamine poisoning caused by P. damselae subsp. damselae. This is the first description of a bacteriophage specifically infecting P. damselae subsp. damselae and its potential applications. Bacteriophage therapy could prove useful in the prevention of histamine poisoning. © 2015 The Society for Applied Microbiology.

  4. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

    Science.gov (United States)

    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption. PMID:26158531

  5. Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells*

    Science.gov (United States)

    Saadane, Aicha; Mast, Natalia; Dao, Tung; Ahmad, Baseer; Pikuleva, Irina A.

    2016-01-01

    The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1−/−Cyp46a1−/− mice. These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1−/−Cyp46a1−/− retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1−/−Cyp46a1−/−Acat1−/− mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function. PMID:27514747

  6. Increased Na+/K(+)-pump activity and adenosine triphosphate utilization after compound 48/80-induced histamine secretion from rat mast cells

    DEFF Research Database (Denmark)

    Johansen, Torben; Praetorius, Birger Hans

    1994-01-01

    The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP) were studied in rat peritoneal mast cells after histamine secretion induced by compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive technique (86Rb+). The ATP content and the glycolytic ATP......-production were measured by the bioluminescence technique (firefly lantern) and by measurement of the lactate production under anaerobic conditions (antimycin A, oligomycin), respectively. There was an increased requirement for ATP after the secretory response associated with an increased activity of the Na+/K(+)-pump....... The anaerobic, but not the aerobic, pathway for ATP-synthesis was able to respond to the increased ATP-requirement. The ATP-requirement of the Na+/K(+)-pump was only partly satisfied when ATP was supplied from either the glycolytic or the oxidative pathway. This may indicate that the availability of ATP...

  7. Cloning and pharmacological characterization of the dog histamine H4 receptor.

    Science.gov (United States)

    Jiang, Wen; Lim, Herman D; Zhang, Mai; Desai, Pragnya; Dai, Heng; Colling, Patricia M; Leurs, Rob; Thurmond, Robin L

    2008-09-11

    The histamine H4 receptor has been shown to have a role in chemotaxis and mediator release in various types of immune cells and has been implicated in mediating inflammation in vivo. Previous work has shown that there were differences in the histamine H4 receptor sequence of different species and these translated into changes in the pharmacology of the receptors. To help further understand the nature of these differences, we have cloned and expressed the histamine H4 receptor of dog (Canis familiaris). The dog histamine H4 receptor has a 61-71% homology with the receptors from other species, with a 71% homology to the human receptor. The affinity for histamine at the dog histamine H4 receptor is 18 nM and is 3-fold lower than the human ortholog. A number of previously described histamine H4 receptor ligands were tested for affinity at the dog histamine H4 receptor and histamine showed the highest affinity of the ligands tested. In addition, the histamine H4 receptor selective antagonist, JNJ 7777120, had a Ki value of 50 nM and acts as an antagonist at the dog receptor. In general, agonists of the human histamine H4 receptor were also agonists of the dog receptor albeit with different efficacy levels. The cloning and in vitro pharmacological characterization of the dog histamine H4 receptor provide useful information for future studies using dog models as well as in understanding the ligand-receptor interactions of the receptor.

  8. Histamine induces NF-κB controlled cytokine secretion by orbital fibroblasts via histamine receptor type-1.

    Science.gov (United States)

    Virakul, Sita; Phetsuksiri, Tanachaporn; van Holten-Neelen, Conny; Schrijver, Benjamin; van Steensel, Leendert; Dalm, Virgil A S H; Paridaens, Dion; van den Bosch, Willem A; van Hagen, P Martin; Dik, Willem A

    2016-06-01

    Mast cells and their products are likely to be involved in regulating orbital fibroblast activity in Graves' Ophthalmopathy (GO). Histamine is abundantly present in granules of mast cells and is released upon mast cell activation. However, the effect of histamine on orbital fibroblasts has not been examined so far. Orbital tissues from GO patients and controls were analyzed for the presence of mast cells using toluidine blue staining and immunohistochemical detection of CD117 (stem cell factor receptor). Orbital fibroblasts were cultured from GO patients and healthy controls, stimulated with histamine and cytokines (IL-6, IL-8, CCL2, CCL5, CCL7, CXCL10 and CXCL11) were measured in culture supernatants. Also hyaluronan levels were measured in culture supernatants and hyaluronan synthase (HAS) and hyaluronidase (HYAL) gene expression levels were determined. In addition, histamine receptor subtype gene expression levels were examined as well as the effect of the histamine receptor-1 (HRH1) antagonist loratadine and NF-κB inhibitor SC-514 on histamine-induced cytokine production. Mast cell numbers were increased in GO orbital tissues. Histamine stimulated the production of IL-6, IL-8 and CCL2 by orbital fibroblasts, while it had no effect on the production of CCL5, CCL7, CXCL10, CXCL11 and hyaluronan. Orbital fibroblasts expressed HRH1 and loratadine and SC-514 both blocked histamine-induced IL-6, IL-8 and CCL2 production by orbital fibroblasts. In conclusion, this study demonstrates that histamine can induce the production of NF-κB controlled-cytokines by orbital fibroblasts, which supports a role for mast cells in GO. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts.

    Science.gov (United States)

    Qin, Zhenwei; Fu, Qiuli; Zhang, Lifang; Yin, Houfa; Jin, Xiuming; Tang, Qiaomei; Lyu, Danni; Yao, Ke

    2016-01-01

    Purpose . It has been confirmed that inflammatory cytokines are involved in the progression of pterygium. Histamine can enhance proliferation and migration of many cells. Therefore, we intend to investigate the proliferative and migratory effects of histamine on primary culture of human pterygium fibroblasts (HPFs). Methods . Pterygium and conjunctiva samples were obtained from surgery, and toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the proliferative rate of HPFs and human conjunctival fibroblasts (HCFs); ki67 expression was also measured by immunofluorescence analysis. Histamine receptor-1 (H1R) antagonist (Diphenhydramine Hydrochloride) and histamine receptor-2 (H2R) antagonist (Nizatidine) were added to figure out which receptor was involved. Wound healing model was used to evaluate the migratory ability of HPFs. Results . The numbers of total mast cells and degranulated mast cells were both higher in pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs and HCFs, the effective concentration (10  μ mol/L) on HPFs was lower than on HCFs (100  μ mol/L), and the effect could be blocked by H1R antagonist. Histamine showed no migratory effect on HPFs. Conclusion . Histamine may play an important role in the proliferation of HPFs and act through H1R.

  10. Histamine and astrocyte function.

    Science.gov (United States)

    Jurič, Damijana M; Kržan, Mojca; Lipnik-Stangelj, Metoda

    2016-09-01

    Astrocytes support the brain through numerous functional interactions in health and disease. The recent advances in our knowledge of astrocyte involvement in various neurological disorders raised up several questions about their role and functioning in the central nervous system. From the evidence discussed in this review, we show that histamine importantly influences the main astrocytic activities such as ion homeostasis, energy metabolism, neurotransmitter clearance, neurotrophic activity and immune response. These processes are mediated through at least three histamine receptor subtypes, H1, H2 and H3, expressed on the astrocyte surface. Thus, we recognize histamine as an important player in the modulation of astrocytic functions that deserves further considerations in exploring involvement of astrocytes in neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Anti-allergic cromones inhibit histamine and eicosanoid release from activated human and murine mast cells by releasing Annexin A1.

    Directory of Open Access Journals (Sweden)

    Samia Yazid

    Full Text Available Although the 'cromones' (di-sodium cromoglycate and sodium nedocromil are used to treat allergy and asthma, their 'mast cell stabilising' mechanism of pharmacological action has never been convincingly explained. Here, we investigate the hypothesis that these drugs act by stimulating the release of the anti-inflammatory protein Annexin-A1 (Anx-A1 from mast cells.We used biochemical and immuno-neutralisation techniques to investigate the mechanism by which cromones suppress histamine and eicosanoid release from cord-derived human mast cells (CDMCs or murine bone marrow-derived mast cells (BMDMCs from wild type and Anx-A1 null mice.CDMCs activated by IgE-FcRε1 crosslinking, released histamine and prostaglandin (PG D2, which were inhibited (30-65% by 5 min pre-treatment with cromoglycate (10 nM or nedocromil (10 nM, as well as dexamethasone (2 nM and human recombinant Anx-A1 (1-10 nM. In CDMCs cromones potentiated (2-5 fold protein kinase C (PKC phosphorylation and Anx-A1 phosphorylation and secretion (3-5 fold. Incubation of CDMCs with a neutralising anti-Anx-A1 monoclonal antibody reversed the cromone inhibitory effect. Nedocromil (10 nM also inhibited (40-60% the release of mediators from murine bone marrow derived-mast cells from wild type mice activated by compound 48/80 and IgE-FcRε1 cross-linking, but were inactive in such cells when these were prepared from Anx-A1 null mice or when the neutralising anti-Anx-A1 antibody was present.We conclude that stimulation of phosphorylation and secretion of Anx-A1 is an important component of inhibitory cromone actions on mast cells, which could explain their acute pharmacological actions in allergy. These findings also highlight a new pathway for reducing mediator release from these cells.

  12. The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

    Directory of Open Access Journals (Sweden)

    Daló Nelson L

    1998-01-01

    Full Text Available Cold acclimatization (4-5°C is accompanied by 2-3 fold increase of brown adipose tissue (BAT. This rapid growth of interscapular BAT was studied after histamine depletion. In control rats maintained at room temperature (28 ± 2°C the BAT histamine content was 23.4 ± 5.9 (mean ± SD µg/g of tissue and cold acclimatization (5±1°C produced a significant increase of BAT weight, but reduced the histamine content to 8.4 ± 1.9 µg/g. The total weight of BAT after 20 days of acclimatization was unaffected by depletion of histamine due to compound 48/80. The low level of histamine in BAT of cold acclimatized rats could be due to a fast rate of amine utilization; alternatively an altered synthesis or storage process may occur during acclimatization.

  13. Histamine formation in flying fish contaminated with Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Hsien-Feng Kung

    2016-06-01

    Full Text Available Abstract Histamine is the main causative agent of scombroid poisoning. However, unlike scombroid fish, histamine poisoning due to consumption of flying fish has never been reported. In this study, the white muscle of flying fish had high levels of free histidine at approximately 423.9 mg/100 g, and was inoculated with Staphylococcus xylosus Q2 isolated from dried flying fish at 5.0 log CFU/g and stored at −20 to 35°C to investigate histamine-related quality. The histamine contents quickly increased to higher than 50 mg/100 g in samples stored at 25 and 35°C within 12 h as well as stored at 15°C within 48 h. However, bacterial growth and histamine formation were controlled by cold storage of the samples at 4°C or below. Once the frozen flying fish samples stored at −20°C for 2 months were thawed and stored at 25°C after 24 h, histamine started to accumulate rapidly (>50 mg/100 g of fish. Therefore, flying fish muscle was a good substrate for histamine formation by bacterial histidine decarboxylation at elevated temperatures (>15°C when it is contaminated with S. xylosus. In conclusion, since the improperly contaminated flying fish muscle with S. xylosus could lead to production of hazardous levels of histamine over time when stored at temperatures >15°C, the flying fish should be stored below 4 °C or below to control proliferation of S. xylosus, and TVBN and histamine production.

  14. Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-δ/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells.

    Science.gov (United States)

    Hattori, Masashi; Mizuguchi, Hiroyuki; Baba, Yuko; Ono, Shohei; Nakano, Tomohiro; Zhang, Qian; Sasaki, Yohei; Kobayashi, Makoto; Kitamura, Yoshiaki; Takeda, Noriaki; Fukui, Hiroyuki

    2013-02-01

    It has been reported that the histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis and H1R expression level strongly correlates with the severity of allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful anti-allergic medications. Recently, we demonstrated that histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the protein kinase Cδ (PKCδ)/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously. Quercetin is one of the well-characterized flavonoids and it possesses many biological activities including anti-allergic activity. However, effect of quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of quercetin on histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized allergy model rats. Quercetin suppressed histamine- and PMA-induced up-regulation of H1R gene expression. Quercetin also inhibited histamine- or PMA-induced phosphorylation of Tyr(311) of PKCδ and translocation of PKCδ to the Golgi. Pre-treatment with quercetin for 3weeks suppressed TDI-induced nasal allergy-like symptoms and elevation of H1R mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that quercetin suppresses H1R gene expression by the suppression of PKCδ activation through the inhibition of its translocation to the Golgi. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Histamine and Antihistamines / Histamin i antihistamini

    Directory of Open Access Journals (Sweden)

    Stojković Nikola

    2015-03-01

    Full Text Available Poslednjih godina beleži se kontinuirani rast prevalencije alergijskih oboljenja. Alergijski imunski odgovor predstavlja jednu kompleksnu mrežu ćelijskih događaja u kojoj učestvuju mnogobrojne imunske ćelije i medijatori. On predstavlja interakciju urođenog i stečenog imunskog odgovora. Ključnu ulogu u imunološkoj kaskadi zauzima histamin, prirodni sastojak tela, koga u alergijskom inflamatornom odgovoru oslobađaju mastociti i bazofili. Cilj ovog rada bio je naglasiti ulogu histamina u alergijskim imunološkim događajima, njegov efekat na Th1 i Th2 subpopulaciju limfocita i produkciju odgovarajućih citokina, kao i ulogu blokatora histamina u tretmanu ovih stanja. Histamin ostvaruje svoj efekat vezivanjem za četiri tipa svojih receptora koji su široko distribuirani u organizmu. Blokatori histamina blokiraju mnogobrojne efekte histamina vezivanjem za ove receptore. Cetirizin, visoko selektivni antihistaminik druge generacije, ne ostvaruje svoje efekte samo vezivanjem za H1 receptore već dovodi do atenuisanja mnogobrojnih zbivanja tokom inflamacijskog procesa. Dobro poznavanje efekata histaminskih blokatora, među njima i cetirizina, može dovesti do pravog odabira terapije u tretmanu alergijskih oboljenja.

  16. Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep

    Science.gov (United States)

    Oikonomou, Grigorios

    2017-01-01

    Abstract Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents. PMID:28275716

  17. Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep.

    Science.gov (United States)

    Chen, Audrey; Singh, Chanpreet; Oikonomou, Grigorios; Prober, David A

    2017-01-01

    Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase ( hdc ) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt -expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt -expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.

  18. Histamine Food Poisoning.

    Science.gov (United States)

    Schirone, Maria; Visciano, Pierina; Tofalo, Rosanna; Suzzi, Giovanna

    2017-01-01

    The consumption of food containing high amounts of histamine and other biogenic amines can cause food poisoning with different symptoms linked to the individual sensitivity and the detoxification activity. Histamine is the only biogenic amine with regulatory limits set by the European Commission in fish and fishery products, because it can lead to a fatal outcome. However, also fermented foods can be involved in outbreaks and sporadic cases of intoxication. The factors affecting the presence of histamine in food are variable and product specific including the availability of the precursor amino acid, the presence of microorganisms producing decarboxylases, and the conditions allowing their growth and enzyme production. Generally, the good quality of raw material and hygienic practices during food processing as well as the use of histidine decarboxylase-negative starter cultures can minimize the occurrence of histamine. Further studies are necessary to estimate the human exposure and the relationship between the total amount of the biogenic amines ingested with food and health effects.

  19. Sensory responses of human skin to synthetic histamine analogues and histamine.

    OpenAIRE

    Davies, M G; Greaves, M W

    1980-01-01

    The potential for itch production in human skin of the synthetic analogues of histamine, 2-methyl histamine (an H1-receptor agonist) and 4-methyl histamine and dimaprit (H2-receptor agonists) has been studied in vivo and compared with histamine. Itch thresholds for 2-methyl histamine were consistently much higher than for histamine (P < 0.001). The H1-receptor antagonist chlorpheniramine raised the itch thresholds to 2-methyl histamine and histamine significantly (P < 0.001). Pruritus was not...

  20. Regulation of the Cardiovascular System by Histamine.

    Science.gov (United States)

    Hattori, Yuichi; Hattori, Kohshi; Matsuda, Naoyuki

    2017-01-01

    Histamine mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in the central nervous system. Histamine also exerts a series of actions upon the cardiovascular system but may not normally play a significant role in regulating cardiovascular function. During tissue injury, inflammation, and allergic responses, mast cells (or non-mast cells) within the tissues can release large amounts of histamine that leads to noticeable cardiovascular effects. Owing to intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H 1 - and H 2 -receptors has become recognized adequately. Besides the recognized H 1 - and H 2 -receptor-mediated cardiovascular responses, novel roles of H 3 - and H 4 -receptors in cardiovascular physiology and pathophysiology have been identified over the last decade. In this review, we describe recent advances in our understanding of cardiovascular function and dysfunction mediated by histamine receptors, including H 3 - and H 4 -receptors, their potential mechanisms of action, and their pathological significance.

  1. Allisonella histaminiformans gen. nov., sp. nov. A novel bacterium that produces histamine, utilizes histidine as its sole energy source, and could play a role in bovine and equine laminitis.

    Science.gov (United States)

    Garner, Matthew R; Flint, Joseph F; Russell, James B

    2002-12-01

    When cattle and horses are fed large amounts of grain, histamine can accumulate in the gastrointestinal tract, and this accumulation can cause an acute inflammation of the hooves (laminitis). When ruminal fluid from dairy cattle fed grain supplements was serially diluted in anaerobic MRS medium containing histidine (50 mM), histamine was detected at dilutions as high as 10(-7). The histidine enrichments were then transferred successively in an anaerobic, carbonate-based medium (50 mM histidine) without glucose. The histamine producing bacteria could not be isolated from the rumens of cattle fed hay; however, histamine producing bacteria could be isolated the feces of cattle fed grain and the cecum of a horse. All of the histamine producing isolates had the same ovoid morphology. The cells stained Gram-negative and were resistant to the ionophore, monensin (25 microM). The doubling time was 110 min, and the yield was 1.5 mg cell protein per mmol histidine. The G+C content was 46.8%. Lysine was the only other amino acid used, but lysine did not allow growth if histidine was absent. Because carbohydrate and organic acid utilization was not detected, it appeared that the isolates used histidine decarboxylation as their sole mechanism of energy derivation. 16s rRNA gene sequencing indicated that the isolates were most closely related to low G+C Gram-positive bacteria (firmicutes), but similarities were < or = 94%. Because the most closely related bacteria (Dialister pneumonsintes, Megasphaera elsdenii and Selenomonas ruminantium) did not produce histamine from histidine, we propose that these histamine producing bacteria be assigned to a new genus, Allisonella, as Allisonella histaminiformans gen. nov., sp. nov. The type strain is MR2 (ATCC BAA610, DSM 15230).

  2. CSF histamine levels in rats reflect the central histamine neurotransmission.

    Science.gov (United States)

    Soya, Atsushi; Song, You Hwi; Kodama, Tohru; Honda, Yoshiko; Fujiki, Nobuhiro; Nishino, Seiji

    2008-01-17

    Reduced cerebrospinal fluid (CSF) histamine levels were found in human hypersomnia. To evaluate the functional significance of changes in CSF histamine levels, we measured the levels in rats across 24h, after the administration of wake-promoting compounds modafinil, amphetamine, and thioperamide, and after sleep deprivation and food deprivation. Thioperamide significantly increased CSF histamine levels with little effects on locomotor activation. Both modafinil and amphetamine markedly increased the locomotor activity, but had no effects on histamine. The levels are high during active period and are markedly elevated by sleep deprivation, but not by food deprivation. Our study suggests that CSF histamine levels in rats reflect the central histamine neurotransmission and vigilance state changes, providing deeper insight into the human data.

  3. Histamine, histamine receptors and antihistamines: new concepts.

    Science.gov (United States)

    Criado, Paulo Ricardo; Criado, Roberta Fachini Jardim; Maruta, Celina W; Machado Filho, Carlos d'Apparecida

    2010-01-01

    Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

  4. The relation between protein synthesis and lipide accumulation in L strain cells and Ehrlich ascites cells.

    Science.gov (United States)

    KING, D W; SOCOLOW, E L; BENSCH, K G

    1959-05-25

    It has long been known that fat accumulates in old injured cells both in tissue culture and in many mammalian disease states. The use of L cells grown in suspension tissue culture permitted the opportunity to study conditions in which lipide accumulation could be retarded or accelerated. These cultures exhibit a three-phase growth curve which is similar to that previously found with bacteria and consists of a lag period, logarithmic growth period, and stationary period. Daily aliquots were removed from cultures going through these phases and protein and cholesterol content correlated with cell division. It was found that L cells gradually accumulated lipide in the cell concurrent with retardation of cell division and protein synthesis. Conversely old lipide-laden cells, placed in fresh media and encouraged to active division with net protein synthesis progressed from a high to a low lipide/cell ratio over a period of 2 to 4 days. An amino acid analogue p-fluorophenylalanine and a mitotic inhibitor, colchicine, also markedly increased the lipide/cell ratio. Similar results were found in in vitro experiments with Ehrlich ascites cells.

  5. Histamine transport and metabolism are deranged in salivary glands in Sjogren's syndrome.

    Science.gov (United States)

    Stegaev, Vasily; Nies, Anne T; Porola, Pauliina; Mieliauskaite, Diana; Sánchez-Jiménez, Francisca; Urdiales, Jóse L; Sillat, Tarvo; Schwelberger, Hubert G; Chazot, Paul L; Katebe, Mwape; Mackiewicz, Zygmunt; Konttinen, Yrjö T; Nordström, Dan C E

    2013-09-01

    To study histamine transport and metabolism of salivary gland (SG) epithelial cells in healthy controls and SS patients. Enzymes and transporters involved in histamine metabolism were analysed in cultured human submandibular salivary gland (HSG) epithelial cells and tissue sections using quantitative real-time PCR and immunostaining. HSG cells were used to study [(3)H]histamine uptake [(±1-methyl-4-phenylpyridinium (MPP)] and efflux by liquid scintillation counting. mRNA levels of l-histidine decarboxylase (HDC) and histamine-N-methyltransferase (HNMT) were similar in the control and SS glands, but diamine oxidase was not expressed at all. Organic cation transporter 3 (OCT3) in healthy SG was localized in the acinar and ductal cells, whereas OCT2 was restricted to the myoepithelial cells. Both transporters were significantly decreased in SS at mRNA and protein levels. OCT3-mRNA levels in HSG cells were significantly higher than those of the other studied transporters. Uptake of [(3)H]histamine was inhibited by MPP in a time-dependent manner, whereas [(3)H]histamine-preloaded HSG cells released it. Ductal epithelial cells are non-professional histamine-producing cells able to release histamine via OCTs at the resting state up to ∼100 nM, enough to excite H3R/H4R(+) epithelial cells, but not H1R, which requires burst release from mast cells. At the stimulated phase, 50-60 μM histamine passes from the interstitial fluid through the acinar cells to saliva, whereas uptake by ductal cells leads to intracellular degradation by HNMT. OCT3/histamine/H4R-mediated cell maintenance and down-regulation of high histamine levels fail in SS SGs.

  6. Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival.

    Science.gov (United States)

    Kim, Nan-Hyung; Lee, Ai-Young

    2010-12-01

    Repigmention of vitiligo requires melanocyte proliferation and migration. Keratinocytes have been shown to play a role in this process. Data from this laboratory showed that bee venom (BV) stimulated melanocyte proliferation and migration as well as melanogenesis. As histamine release is associated with BV, its effect on melanocyte proliferation and migration was examined. Cultured normal human melanocytes treated with histamine were studied with and without receptor-specific antagonists or agonists. The effect of histamine on vitiliginous keratinocytes, in cultured cells treated with a PI3K inhibitor in the presence of TNF-α, was also examined. Histamine exerted a more significant effect on melanocyte proliferation than on melanogenesis. This occurred through the H2 receptor with complex signalling to ERK, CREB, and Akt activation, which stimulated melanocyte migration. Histamine and the H2 receptor agonist also increased survival of vitiliginous, but not normal, keratinocytes, with NF-κB activation. Because expression levels of the H2 receptor was significantly decreased in depigmented compared to normally pigmented epidermis, in patients with vitiligo, histamine may increase the survival of vitiliginous keratinocytes. Overall, histamine stimulated the proliferation and migration of melanocytes and the vitiliginous keratinocyte survival, providing the basis for novel therapeutic approaches to vitiligo repigmentation. © 2010 John Wiley & Sons A/S.

  7. Interactions of the histamine and hypocretin systems in CNS disorders.

    Science.gov (United States)

    Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

    2015-07-01

    Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

  8. Effect of histamine on contractile activity of smooth muscles in bovine mesenteric lymph nodes.

    Science.gov (United States)

    Lobov, G I; Pan'kova, M N

    2012-02-01

    The effects of histamine and mechanisms of its action on the capsular smooth muscle cells of mesenteric lymph nodes were examined on isolated capsular strips under isometric conditions. Histamine (1×10(-8)-5×10(-7) M) decreased the tone of capsular smooth muscle cells and the frequency of phasic contractions. At high concentrations (more than 5×10(-6) M), histamine increased the amplitude and frequency of phasic contractions against the background of increased tonic stress. The effects of histamine were dose-dependent and were realized via direct stimulation of H(1)- and H(2)-receptors on the membrane of smooth muscle cells.

  9. Reporter cell lines for detection of pertussis toxin in acellular pertussis vaccines as a functional animal-free alternative to the in vivo histamine sensitization test.

    Science.gov (United States)

    Hoonakker, Marieke E; Verhagen, Lisa M; van der Maas, Larissa; Sloots, Arjen; Hendriksen, Coenraad F M

    2017-02-22

    Detoxified pertussis toxin (pertussis toxoid) is a major antigen in acellular pertussis vaccines. Testing these vaccines on the presence of residual pertussis toxin (PTx) and reversion to toxicity is performed by the regulatory required in vivo Histamine Sensitization test (HIST). Lack of mechanistic understanding of the HIST, technical handicaps and animal welfare concerns, have promoted the development of alternative methods. As the majority of the cellular effects of PTx depend on its ability to activate intracellular pathways involving cAMP, the in vitro cAMP-PTx assay was developed. Although this assay could be used to detect PTx activity, it lacked sensitivity and robustness for use in a quality control setting. In the present study, novel reporter cell lines (CHO-CRE and A10-CRE) were generated that stably express a reporter construct responsive to changes in intracellular cAMP levels. These reporter cell lines were able to detect PTx in a concentration-dependent manner when combined with fixed amounts of forskolin. The CHO-CRE cell line enabled detection of PTx in the context of a multivalent vaccine containing aP, with a sensitivity equal to the HIST. However, the sensitivity of the A10-CRE cells was insufficient for this purpose. The experiments also suggest that the CHO-CRE reporter cell line might be suitable for assessment of cellular effects of PTd reverted to PTx. The CHO-CRE reporter cell line provides a platform that meets the criteria for specificity and sensitivity and is a promising in vitro model with potential to replace the HIST. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Analytical Methods for the Quantification of Histamine and Histamine Metabolites.

    Science.gov (United States)

    Bähre, Heike; Kaever, Volkhard

    2017-01-01

    The endogenous metabolite histamine (HA) is synthesized in various mammalian cells but can also be ingested from exogenous sources. It is involved in a plethora of physiological and pathophysiological processes. So far, four different HA receptors (H 1 R-H 4 R) have been described and numerous HAR antagonists have been developed. Contemporary investigations regarding the various roles of HA and its main metabolites have been hampered by the lack of highly specific and sensitive analytic methods for all of these analytes. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is the method of choice for identification and sensitive quantification of many low-molecular weight endogenous metabolites. In this chapter, different methodological aspects of HA quantification as well as recommendations for LC-MS/MS methods suitable for analysis of HA and its main metabolites are summarized.

  11. Sustained accumulation of antigen-presenting cells after infection promotes local T-cell immunity.

    Science.gov (United States)

    Collins, Nicholas; Hochheiser, Katharina; Carbone, Francis R; Gebhardt, Thomas

    2017-11-01

    Antigen-presenting cells (APC), such as dendritic cells (DC) and macrophages, are critical for T-cell-mediated immunity. Although it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of DCs and macrophages. These APC are found at elevated numbers at sites of resolved infection or inflammation compared with unaffected regions of skin. Importantly, this local accumulation of APC is sustained for prolonged periods of time and has important functional consequences, as it promotes interferon-γ responses by virus-specific CD4 + T cells upon localized challenge infection with HSV-1. Thus, our results highlight how infection history determines long-term changes in immune cell composition in skin and how different types of immune cells accumulate, persist and co-operate to provide optimal immunity at this critical barrier site.

  12. Radioprotective potential of histamine on rat small intestine and uterus

    Science.gov (United States)

    Carabajal, E.; Massari, N.; Croci, M.; Martinel Lamas, D.; Prestifilippo, J.P.; Ciraolo, P.; Bergoc, R.M.; Rivera, E.S.; Medina, V.A.

    2012-01-01

    The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239±12 vs 160±10; Phistamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radio-protective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials. PMID:23361244

  13. Anti-histaminic potentials of Cnidoscolus aconitifolius in the ...

    African Journals Online (AJOL)

    Similarly, the observable significant reduction in the paw size was comparable to the Ibuprofen (100 mg/kg). Different concentrations of EECA (0.025, 0.05, 0.1 and 0.2 mg/kg) were assessed on the histamine release from the mast cells. The rats administered with 0.2mg/kg had the most profound effects on the histamine ...

  14. Histamine induces the production of matrix metalloproteinase-9 in human astrocytic cultures via H1-receptor subtype.

    Science.gov (United States)

    Patel, Aarti; Vasanthan, Vishnu; Fu, Wen; Fahlman, Richard P; MacTavish, David; Jhamandas, Jack H

    2016-05-01

    Accumulation of β-amyloid (Aβ) protein within the brain is a neuropathological hallmark of Alzheimer's disease (AD). One strategy to facilitate Aβ clearance from the brain is to promote Aβ catabolism. Matrix metalloproteinase-9 (MMP-9), a member of the family of Zn(+2)-containing endoproteases, known to be expressed and secreted by astrocytes, is capable of degrading Aβ. Histamine, a major aminergic brain neurotransmitter, stimulates the production of MMP-9 in keratinocytes through the histamine H1 receptor (H1R). In the present study, we show that histamine evokes a concentration- and calcium-dependent release of MMP-9 from human astrocytic U373 cells and primary cultures of human and rat astrocytes through the H1R subtype. Activation of H1R on astrocytes elevated intracellular levels of Ca(2+) that was accompanied by time-dependent increases in MAP kinase p44/p42 and PKC. In-cell western blots revealed dose-dependent increases in both enzymes, confirming involvement of these signal transduction pathways. We next investigated the extent of recombinant human MMP-9 (rhMMP-9) proteolytic activity on soluble oligomeric Aβ (soAβ). Mass spectrometry demonstrated time-dependent cleavage of soAβ (20 μM), but not another amyloidogenic protein amylin, upon incubation with rhMMP-9 (100 nM) at 1, 4 and 17 h. Furthermore, Western blots showed a shift in soAβ equilibrium toward lower order, less toxic monomeric species. In conclusion, both MAPK p44/p42 and PKC pathways appear to be involved in histamine-upregulated MMP-9 release via H1Rs in astrocytes. Furthermore, MMP-9 appears to cleave soAβ into less toxic monomeric species. Given the key role of histamine in MMP-9 release, this neurotransmitter may serve as a potential therapeutic target for AD.

  15. Effect of H4R antagonist N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamides and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole on histamine and 4-methylhistamine-induced mast cell response.

    Science.gov (United States)

    Nagarajan, Gomathi; Mariappanadar, Vairamani; Tamizh, Muthu; Kaliappan, Ilango; Elden, Berla Thangam

    2017-06-01

    The histamine plays a decisive role in acute and chronic inflammatory responses and is regulated through its four types of distinct receptors designated from H1 to H4. Recently histamine 4 receptor (H4R) antagonists have been reported to possess various pharmacological effects against various allergic diseases. To investigate the inhibitory effect of N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamide (Compound A) and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole (Compound L) on H4R-mediated calcium mobilization, cytokine IL-13 production, ERK1/2, Akt and NF-κB activation in human mastocytoma cells-1 (HMC-1). Compounds A and L were synthesized chemically and their inhibitory effect on intracellular calcium release was analyzed by Fluo-4 calcium assay, cytokine measurement through ELISA and activation of signaling molecules by western blot. Pre-treatment with compounds A and L significantly reduced the H4R-mediated intracellular calcium release. Histamine and 4-methylhistamine (4-MH) induced Th2 cytokine IL-13 production in HMC-1 cells, was inhibited by compound A (77.61%, 74.25% at 1 μM concentration) and compound L (79.63%, 81.70% at 1 μM concentration). Furthermore, histamine induced the phosphorylation of ERK1/2, Akt and NF-κB was suppressed by compounds A and L at varying levels, ERK1/2 (88%, 86%), Akt (88%, 89%) and NF-κB (89%, 87%) in HMC-1 cells. Taken together these data demonstrate that compound A and compound L may block H4R-mediated downstream signaling events.

  16. Histamine therapeutic efficacy in metastatic melanoma: Role of histamine H4 receptor agonists and opportunity for combination with radiation.

    Science.gov (United States)

    Massari, Noelia A; Nicoud, Melisa B; Sambuco, Lorena; Cricco, Graciela P; Martinel Lamas, Diego J; Herrero Ducloux, María V; Blanco, Horacio; Rivera, Elena S; Medina, Vanina A

    2017-04-18

    The aims of the work were to improve our knowledge of the role of H4R in melanoma proliferation and assess in vivo the therapeutic efficacy of histamine, clozapine and JNJ28610244, an H4R agonist, in a preclinical metastatic model of melanoma. Additionally, we aimed to investigate the combinatorial effect of histamine and gamma radiation on the radiobiological response of melanoma cells.Results indicate that 1205Lu metastatic melanoma cells express H4R and that histamine inhibits proliferation, in part through the stimulation of the H4R, and induces cell senescence and melanogenesis. Daily treatment with H4R agonists (1 mg/kg, sc) exhibited a significant in vivo antitumor effect and importantly, compounds reduced metastatic potential, particularly in the group treated with JNJ28610244, the H4R agonist with higher specificity. H4R is expressed in benign and malignant lesions of melanocytic lineage, highlighting the potential clinical use of histamine and H4R agonists. In addition, histamine increased radiosensitivity of melanoma cells in vitro and in vivo. We conclude that stimulation of H4R by specific ligands may represent a novel therapeutic strategy in those tumors that express this receptor. Furthermore, through increasing radiation-induced response, histamine could improve cancer radiotherapy for the treatment of melanoma.

  17. Influence of histamine of precursors of granulocytic leukocytes in murine bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Nakaya, N.; Tasaka, K.

    1988-01-01

    The effect of histamine on granulocytic progenitor cells in murine bone marrow was studied in vitro. When bone marrow cells were cultured for three days with the drug, 10/sup -8/ M to 10/sup -5/ M of histamine stimulated differentiation and proliferation of myeloid precursor cells. Subsequently, the number of descendant cells, such as metamyelocytes and neutrophils, increased dose-dependently. Co-existence of equimolar H/sub 2/ blockers such as cimetidine and ranitidine completely suppressed this effect of histamine, though this was not the case with an H/sub 1/ blocker/histamine combination. Significant increase in /sup 3/H-thymidine incorporation was observed almost exclusively in myeloblasts, promyelocytes and myelocytes after exposure to histamine at concentrations higher than 10/sup -8/ M. Also, selective incorporation of /sup 3/H-histamine into bone marrow cells was observed in myeloblasts and promyelocytes, but histamine incorporation was not influenced by the presence of either of histamine agonists of antagonists. While histamine, via H/sub 2/ receptors, selectively increased the number of granulocytic colony forming units in culture (CFU-C), it had no such effect on macrophage colonies. 22 references, 5 figures, 4 tables.

  18. Effect of histamine on the growth of human gastrointestinal tumours: reversal by cimetidine.

    OpenAIRE

    Watson, S A; Wilkinson, L J; Robertson, J F; Hardcastle, J D

    1993-01-01

    The proliferative effects of histamine were examined on the human gastric tumour cell lines; MKN45, the gastrin producing subline, MKN45G, and the colorectal lines; LoVo and C170. The proliferation of MKN45 as assessed by 75[Se] selenomethionine uptake and cell counts was increased by histamine concentrations of 10(-7) and 10(-9) M. Histamine concentrations between 10(-6) and 10(-7) M maximally stimulated MKN45G proliferation which titrated out at lower histamine concentrations. The accumulat...

  19. CSF histamine levels in rats reflect the central histamine neurotransmission

    OpenAIRE

    Soya, Atsushi; Song, You Hwi; Kodama, Tohru; Honda, Yoshiko; Fujiki, Nobuhiro; Nishino, Seiji

    2007-01-01

    Reduced cerebrospinal fluid (CSF) histamine levels were found in human hypersomnia. To evaluate the functional significance of changes in CSF histamine levels, we measured the levels in rats across 24 h, after the administration of wake-promoting compounds modafinil, amphetamine, and thioperamide, and after sleep deprivation and food deprivation.

  20. The influence of cholinergic agents on histamine release from HMC-1 human mast cell line stimulated with IgG, C-reactive protein and compound 48/80.

    Science.gov (United States)

    Nazarov, Peter G; Pronina, Anastasia P

    2012-11-27

    The aim of this work is to study the role of acetylcholine (ACh) receptors (AChRs) in the regulation of FcγR activity in human mast cells (MC) activated by aggregated IgG (aIgG) and CRP. MC, the key regulators at the interface of innate and acquired immunity, have abundant Fc receptors for IgG (FcγRII) which indicate the role of their ligands, IgG and C-reactive protein (CRP), in regulating MC activity. Cholinergic control of FcγR-dependent MC functions is poorly defined. HMC-1 culture of human MC; cell incubations with cholinergic drugs and FcγR ligands such as heat aggregated human IgG or purified human CRP; compound 48/80, a known histamine liberator employing G protein-coupled receptors, was used as a positive control of MC degranulation; assessment of histamine release. Both nAChR and mAChR antagonists (hexamethonium and methacine, respectively), per se, elevated histamine-releasing activity of the HMC-1 and suppressed the MC responses to most of investigated activators (carbachol, compound 48/80, and to a lesser extent aIgG). Two blockers together should be applied to aIgG-stimulated cells in order to obtain appreciable suppression of histamine release. The FcγR-mediated HMC-1 cell response to CRP was the least sensitive to attenuation by ACh signaling. The data obtained suggest the involvement of ACh in the functioning of other receptor systems. Our results indicate that AChRs are closely associated with G protein-coupled receptor-induced reactions of MC and optionally with FcγR-dependent functions. The data presented demonstrate that AChRs and endogenous ACh are involved in regulating mast cell degranulation and histamine release by affecting the functions of receptors to compound 48/80 and, less, FcγRs. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro.

    Science.gov (United States)

    Shoji, Naruo; Asano, Kazuhito; Furuta, Atsuko; Hirano, Kojiro; Suzaki, Harumi

    2011-01-01

    Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H(1) receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-κB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions. Copyright © 2010 S. Karger AG, Basel.

  2. Histamine selectively potentiates acid-sensing ion channel 1a.

    Science.gov (United States)

    Nagaeva, Elina I; Tikhonova, Tatiana B; Magazanik, Lev G; Tikhonov, Denis B

    2016-10-06

    Although acid-sensitive ion channels (ASICs) play an important role in brain functions, the exact mechanism of their physiological activation remain unclear. A possible answer to the intriguing question is that some presently unknown endogenous ligand(s) positively modulate ASICs and enhance their responses to physiologically significant level. In the present work we found that histamine selectively potentiates ASIC1a homomers in CHO cells. Action of histamine was particularly pronounced at modest acidifications, which cause minor response. At these conditions micromolar concentrations of histamine have provided significant potentiation of ASIC1a response. We proposed that histamine and possibly some other endogenous amines can positively modulate ASICs functions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis.

    Science.gov (United States)

    Miyano, Kyohei; Matsushita, Sho; Tsuchida, Tetsuya; Nakamura, Koichiro

    2016-09-01

    We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD. © 2016 Japanese Dermatological Association.

  4. Histamine: a new immunomodulatory player in the neuron-glia crosstalk

    Directory of Open Access Journals (Sweden)

    Sandra M Rocha

    2014-04-01

    Full Text Available Histamine is an amine acting as a major peripheral inflammatory mediator. In the brain, histamine was initially viewed as a neurotransmitter, but new evidences support its involvement in the modulation of innate immune responses. Recently, we showed that histamine modulates microglial migration and cytokine release. Its pleiotropic actions, ranging from neurotransmission to inflammation, highlight histamine as a key player in a vast array of brain physiologic activities and also in the pathogenesis of several neurodegenerative diseases. Herein, we emphasize the role of histamine as a modulator of brain immune reactions, either by acting on invading peripheral immune cells and/or on resident microglial cells. We also unveil the putative involvement of histamine in the microglial-neuronal communication. We first show that histamine modulates the release of inflammatory mediators, namely nitric oxide, by microglia cells. Consequently, the microglia secretome released upon histamine stimulation fosters dopaminergic neuronal death. These data may reveal important new pharmacological applications on the use histamine and antihistamines, particularly in the context of Parkinson’s disease.

  5. Histamine stimulates neurogenesis in the rodent subventricular zone.

    Science.gov (United States)

    Bernardino, Liliana; Eiriz, Maria Francisca; Santos, Tiago; Xapelli, Sara; Grade, Sofia; Rosa, Alexandra Isabel; Cortes, Luísa; Ferreira, Raquel; Bragança, José; Agasse, Fabienne; Ferreira, Lino; Malva, João O

    2012-04-01

    Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell-based therapies. Herein, we describe a unique role of histamine in inducing functional neuronal differentiation from cultured mouse SVZ stem/progenitor cells. This proneurogenic effect depends on histamine 1 receptor activation and involves epigenetic modifications and increased expression of Mash1, Dlx2, and Ngn1 genes. Biocompatible poly (lactic-co-glycolic acid) microparticles, engineered to release histamine in a controlled and prolonged manner, also triggered robust neuronal differentiation in vitro. Preconditioning with histamine-loaded microparticles facilitated neuronal differentiation of SVZ-GFP cells grafted in hippocampal slices and in in vivo rodent brain. We propose that neuronal commitment triggered by histamine per se or released from biomaterial-derived vehicles may represent a new tool for brain repair strategies. Copyright © 2012 AlphaMed Press.

  6. Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.

    Science.gov (United States)

    Tsai, Chung-Che; Kuo, Ting-Yu; Hong, Zhi-Wei; Yeh, Ying-Chieh; Shih, Kuo-Shun; Du, Shin-Yi; Fu, Hua-Wen

    2015-01-01

    Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.

  7. Arrhythmogenic effect of sympathetic histamine in mouse hearts subjected to acute ischemia.

    Science.gov (United States)

    He, Gonghao; Hu, Jing; Li, Teng; Ma, Xue; Meng, Jingru; Jia, Min; Lu, Jun; Ohtsu, Hiroshi; Chen, Zhong; Luo, Xiaoxing

    2012-02-10

    The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell-deficient mice (MCDM) and histidine decarboxylase knockout (HDC(-/-)) mice were used to exclude the potential involvement of mast cells. Electrical field stimulation and acute ischemia-reperfusion evoked chemical sympathectomy-sensitive histamine release from the hearts of both MCDM and wild-type (WT) mice but not from HDC(-/-) mice. The release of histamine from the hearts of MCDM and WT mice was associated with the development of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. The incidence and duration of induced ventricular arrhythmias were found to decrease in the presence of the selective histamine H(2) receptor antagonist famotidine. Additionally, the released histamine facilitated the arrhythmogenic effect of simultaneously released norepinephrine. We conclude that, under acute ischemic conditions, cardiac sympathetic histamine released by overactive sympathetic nerve terminals plays a certain arrhythmogenic role via H(2) receptors. These findings provided novel insight into the pathophysiological roles of sympathetic histamine, which may be a new therapeutic target for acute ischemia-induced arrhythmias.

  8. Modulation of ConA-induced inflammatory ascites by histamine - short communication.

    Science.gov (United States)

    Baintner, Károly

    2015-03-01

    The early phase of the ConA-induced inflammatory ascites was studied, with special reference to histamine. Concanavalin A (ConA), a cell-surface binding lectin was injected i.p. (25 mg/kg bw) to mice. After 1 h the animals were killed, the ascitic fluid collected and measured. Other agents were injected s.c., 10 min before the ConA-challenge. Exogenous histamine markedly inhibited the ConA-induced ascites. Release of endogenous vasoactive agents from the mast cells by Compound 48/80 had a similar, but slight effect. Cromolyn, a mast cell stabilizing agent, and chloropyramine, a histamine H1 receptor antagonist was ineffective. Although histamine increases endothelial permeability, it did not enhance the formation of ascitic fluid, on the contrary, it inhibited the ConA-induced ascites, presumably due to its known hypotonic effect. It is concluded that ConA-induced ascites is not mediated by mast cell histamine.

  9. Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

    Science.gov (United States)

    Martinel Lamas, Diego J; Cortina, Jorge E; Ventura, Clara; Sterle, Helena A; Valli, Eduardo; Balestrasse, Karina B; Blanco, Horacio; Cremaschi, Graciela A; Rivera, Elena S; Medina, Vanina A

    2015-01-01

    The radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine or its receptor ligands and gamma radiation in vitro on the radiobiological response of 2 breast cancer cell lines (MDA-MB-231 and MCF-7), to explore the potential molecular mechanisms of the radiosensitizing action and to evaluate the histamine-induced radiosensitization in vivo in a triple negative breast cancer model. Results indicate that histamine significantly increased the radiosensitivity of MDA-MB-231 and MCF-7 cells. This effect was mimicked by the H1R agonist 2-(3-(trifluoromethyl)phenyl)histamine and the H4R agonists (Clobenpropit and VUF8430) in MDA-MB-231 and MCF-7 cells, respectively. Histamine and its agonists enhanced radiation-induced oxidative DNA damage, DNA double-strand breaks, apoptosis and senescence. These effects were associated with increased production of reactive oxygen species, which correlated with the inhibition of catalase, glutathione peroxidase and superoxide dismutase activities in MDA-MB-231 cells. Histamine was able also to potentiate in vivo the anti-tumoral effect of radiation, increasing the exponential tumor doubling time. We conclude that histamine increased radiation response of breast cancer cells, suggesting that it could be used as a potential adjuvant to enhance the efficacy of radiotherapy. PMID:25482934

  10. Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer.

    Science.gov (United States)

    Martinel Lamas, Diego J; Cortina, Jorge E; Ventura, Clara; Sterle, Helena A; Valli, Eduardo; Balestrasse, Karina B; Blanco, Horacio; Cremaschi, Graciela A; Rivera, Elena S; Medina, Vanina A

    2015-01-01

    The radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine or its receptor ligands and gamma radiation in vitro on the radiobiological response of 2 breast cancer cell lines (MDA-MB-231 and MCF-7), to explore the potential molecular mechanisms of the radiosensitizing action and to evaluate the histamine-induced radiosensitization in vivo in a triple negative breast cancer model. Results indicate that histamine significantly increased the radiosensitivity of MDA-MB-231 and MCF-7 cells. This effect was mimicked by the H1R agonist 2-(3-(trifluoromethyl)phenyl)histamine and the H4R agonists (Clobenpropit and VUF8430) in MDA-MB-231 and MCF-7 cells, respectively. Histamine and its agonists enhanced radiation-induced oxidative DNA damage, DNA double-strand breaks, apoptosis and senescence. These effects were associated with increased production of reactive oxygen species, which correlated with the inhibition of catalase, glutathione peroxidase and superoxide dismutase activities in MDA-MB-231 cells. Histamine was able also to potentiate in vivo the anti-tumoral effect of radiation, increasing the exponential tumor doubling time. We conclude that histamine increased radiation response of breast cancer cells, suggesting that it could be used as a potential adjuvant to enhance the efficacy of radiotherapy.

  11. Histamine 50-Skin-Prick Test: A Tool to Diagnose Histamine Intolerance

    OpenAIRE

    Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

    2011-01-01

    Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and ...

  12. Histamine Formation in a Dry Salted Twaite Shad ( Alosa fallax lacustris ) Product.

    Science.gov (United States)

    Vasconi, Mauro; Bellagamba, Federica; Bernardi, Cristian; Martino, Piera Anna; Moretti, Vittorio Maria

    2017-01-01

    Landlocked shad is a freshwater clupeid fish ( Alosa fallax lacustris ) whose consumption is associated with the risk of scombrotoxin poisoning. Traditionally, fresh shad are subjected to an artisanal processing procedure, consisting of dry salting and maturation under pressure, to give a fish product named missoltino , which is stored in large metallic barrels and is sold to local consumers and restaurants. In recent years, the introduction of modern food packaging technologies has enabled this product to also be distributed in shops and supermarkets. Consequently, the determination of the safety of this product is an urgent issue. The aims of the present research were to measure histamine levels and histamine-forming bacteria in shad products collected at different phases of preparation and ripening, in order to minimize poison hazards, to provide technical information about risk, and to standardize the production process. One hundred twenty-six samples of shad (21 fresh fish and 105 dried) at different phases of preparation and ripening were collected from seven producers and were analyzed for chemical composition, histamine content, and microbiological properties. After 130 days of ripening, samples from three producers presented unacceptable amounts of histamine (>200 mg/kg), according to European Union legislation. A moderate negative correlation was found between histamine levels and salt content (r =-0.504, P histamine levels and water phase salt content (r =-0.415, P histamine. The most effective preventive measures for histamine formation and accumulation in salted shad were strictly related to fish handling and storage conditions during processing.

  13. Microbial cells as biosorbents for heavy metals: accumulation of Uranium by Saccharomyces cerevisiae and Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Strandberg, G.W.; Shumate, S.E. II; Parrott, J.R. Jr.

    1981-01-01

    Uranium accumulated extracellularly on the surfaces of Saccharomyces cerevisiae cells. The rate and extent of accumulation were subject to environmental parameters, such as pH, temperature, and interference by certain anions and cations. Uranium accumulation by Pseudomonas aeruginosa occurred intracellularly and was extremely rapid (<10 s), and no response to environmental parameters could be detected. Metabolism was not required for metal uptake by either organism. Cell-bound uranium reached a concentration of 10 to 15% of the dry cell weight, but only 32% of the S. cerevisiae cells and 44% of the P. aeruginosa cells within a given population possessed visible uranium deposits when examined by electron microscopy. Rates of uranium uptake by S. cerevisiae were increased by chemical pretreatment of the cells. Uranium could be removed chemically from S. cerevisiae cells, and the cells could then be reused as a biosorbent

  14. Effects of high levels of dietary zinc oxide on ex vivo epithelial histamine response and investigations on histamine receptor action in the proximal colon of weaned piglets.

    Science.gov (United States)

    Kröger, S; Pieper, R; Aschenbach, J R; Martin, L; Liu, P; Rieger, J; Schwelberger, H G; Neumann, K; Zentek, J

    2015-11-01

    The aim of the study was to identify the effect of high dietary zinc oxide (ZnO) levels on the histamine-induced secretory-type response and histamine metabolism in the porcine proximal colon. After weaning at d 26, 3 diets with low (LZn), normal (NZn), and high (HZn) concentrations of zinc (57, 164, or 2,425 mg/kg) were fed to a total of 120 piglets. Digesta and tissue samples were taken from the ascending colon after 7 ± 1, 14 ± 1, 21 ± 1, and 28 ± 1 d. Partially stripped tissue was mounted in Ussing chambers, and histamine was applied either to the serosal or mucosal compartments. Tissue was pretreated with or without aminoguanidine and amodiaquine to block the histamine-degrading enzymes diamine oxidase (DAO) and histamine -methyltransferase (HMT), respectively. Gene expression and catalytic activity of DAO and HMT in the tissue were analyzed. The numbers of mast cells were determined in tissue samples, and histamine concentration was measured in the colon digesta. Colon tissue from another 12 piglets was used for functional studies on histamine H and H receptors by using the neuronal conduction blocker tetrodotoxin (TTX) and the H and H receptor blocker chloropyramine and famotidine, respectively. After serosal histamine application to colonic tissue in Ussing chambers, the change of short-circuit current (Δ) was not affected by pretreatment and was not different between Zn feeding groups. The Δ after mucosal histamine application was numerically lower ( = 0.168) in HZn compared to LZn and NZn pigs. Mast cell numbers increased from 32 to 46 d of life ( histamine response was partly inhibited by chloropyramine or famotidine ( histamine tended to be decreased when chloropyramine but not famotidine was applied from either the serosal or the mucosal side ( = 0.055). Tetrodotoxin alone or in combination with chloropyramine resulted in a similar reduction in the mucosal histamine response ( histamine metabolism on dietary ZnO oversupplementation. For the first

  15. Heterogeneous effects of histamine on proliferation of lung- and blood-derived T-cell clones from healthy and asthmatic persons

    NARCIS (Netherlands)

    Hol, B. E.; Krouwels, F. H.; Bruinier, B.; Lutter, R.; Bast, A.; Wierenga, E. A.; Jansen, H. M.; Out, T. A.

    1993-01-01

    We have studied the effects of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment

  16. Histamine and tryptase in nasal lavage fluid after allergen challenge

    DEFF Research Database (Denmark)

    Jacobi, H H; Skov, P S; Poulsen, L K

    1999-01-01

    BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine...... the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...

  17. Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine.

    Science.gov (United States)

    Linares, Daniel M; del Rio, Beatriz; Redruello, Begoña; Ladero, Victor; Martin, M Cruz; Fernandez, Maria; Ruas-Madiedo, Patricia; Alvarez, Miguel A

    2016-04-15

    Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

    1998-01-01

    OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

  19. Synergistic mucus secretion by histamine and IL-4 through TMEM16A in airway epithelium.

    Science.gov (United States)

    Kang, Ju Wan; Lee, Yong Hyuk; Kang, Min Jeong; Lee, Hyun Jae; Oh, Ryung; Min, Hyun Jin; Namkung, Wan; Choi, Jae Young; Lee, Sang Nam; Kim, Chang-Hoon; Yoon, Joo-Heon; Cho, Hyung-Ju

    2017-09-01

    Histamine is an important mediator of allergic reactions, and mucus hypersecretion is a major allergic symptom. However, the direct effect of histamine on mucus secretion from airway mucosal epithelia has not been clearly demonstrated. TMEM16A is a Ca 2+ -activated chloride channel, and it is closely related to fluid secretion in airway mucosal epithelia. We investigated whether histamine directly induces fluid secretion from epithelial cells or submucosal glands (SMG) and mechanisms related, therewith, in allergic airway diseases. In pig airway tissues from the nose or trachea, histamine was a potent secretagogue that directly induced strong responses. However, gland secretion from human nasal tissue was not induced by histamine, even in allergic rhinitis patients. Histamine type 1 receptor (H1R) and histamine type 2 receptor (H2R) were not noted in SMG by in situ hybridization. Cultured primary human nasal epithelial (NHE) cells were used for the measurement of short-circuit current changes with the Ussing chamber. Histamine-induced slight responses of anion secretions under normal conditions. The response was enhanced by IL-4 stimulation through TMEM16A, which might be related to fluid hypersecretion in allergic rhinitis. Pretreatment with IL-4 augmented the histamine response that was suppressed by a TMEM16A inhibitor. TMEM16A expression was enhanced by 24-h treatment of IL-4 in human nasal epithelial cells. The expression of TMEM16A was significantly elevated in an allergic rhinitis group, compared with a control group. We elucidated histamine-induced fluid secretions in synergy with IL-4 through TMEM16A in the human airway epithelium. In addition, we observed species differences between pigs and humans in terms of gland secretion of histamine. Copyright © 2017 the American Physiological Society.

  20. A new cultivation method for microbial oil production: cell pelletization and lipid accumulation by Mucor circinelloides

    Directory of Open Access Journals (Sweden)

    Zhang Weidong

    2011-06-01

    Full Text Available Abstract The recent energy crisis has triggered significant attention on the microbial synthesis of lipids, which comprise the raw material for biodiesel production. Microbial oil accumulation with filamentous fungi has great potential because filamentous fungi can form pellets during cell growth, and these pellets are much easier to harvest from cell broth. This paper focuses on the cell pelletization process of the oleaginous Mucor circinelloides. We have studied the effect of various cultural conditions on pelletized cell growth and lipid accumulation. This study is the first to report that pH adjustment during cell growth plays a key role in pellet formation of M. circinelloides and describes a handy method by which to induce cell pelletization in submerged fungal cultivation. Our study reveals that cell growth and lipid production are not significantly affected by pelletization and that lipid accumulation is triggered at stressed conditions, such as a high carbon-to-nitrogen ratio and high temperature.

  1. A new cultivation method for microbial oil production: cell pelletization and lipid accumulation by Mucor circinelloides.

    Science.gov (United States)

    Xia, Chunjie; Zhang, Jianguo; Zhang, Weidong; Hu, Bo

    2011-06-02

    The recent energy crisis has triggered significant attention on the microbial synthesis of lipids, which comprise the raw material for biodiesel production. Microbial oil accumulation with filamentous fungi has great potential because filamentous fungi can form pellets during cell growth, and these pellets are much easier to harvest from cell broth. This paper focuses on the cell pelletization process of the oleaginous Mucor circinelloides. We have studied the effect of various cultural conditions on pelletized cell growth and lipid accumulation. This study is the first to report that pH adjustment during cell growth plays a key role in pellet formation of M. circinelloides and describes a handy method by which to induce cell pelletization in submerged fungal cultivation. Our study reveals that cell growth and lipid production are not significantly affected by pelletization and that lipid accumulation is triggered at stressed conditions, such as a high carbon-to-nitrogen ratio and high temperature.

  2. Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster

    Science.gov (United States)

    Kis, Viktor; Barti, Benjámin; Lippai, Mónika; Sass, Miklós

    2015-01-01

    Lipid droplets (LDs) are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain’s LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp), as we have demonstrated through light- and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain. PMID:26148013

  3. Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster.

    Science.gov (United States)

    Kis, Viktor; Barti, Benjámin; Lippai, Mónika; Sass, Miklós

    2015-01-01

    Lipid droplets (LDs) are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain's LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp), as we have demonstrated through light- and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain.

  4. Triacylglycerol Accumulation in Photosynthetic Cells in Plants and Algae.

    Science.gov (United States)

    Du, Zhi-Yan; Benning, Christoph

    2016-01-01

    Plant and algal oils are some of the most energy-dense renewable compounds provided by nature. Triacylglycerols (TAGs) are the major constituent of plant oils, which can be converted into fatty acid methyl esters commonly known as biodiesel. As one of the most efficient producers of TAGs, photosynthetic microalgae have attracted substantial interest for renewable fuel production. Currently, the big challenge of microalgae based TAGs for biofuels is their high cost compared to fossil fuels. A conundrum is that microalgae accumulate large amounts of TAGs only during stress conditions such as nutrient deprivation and temperature stress, which inevitably will inhibit growth. Thus, a better understanding of why and how microalgae induce TAG biosynthesis under stress conditions would allow the development of engineered microalgae with increased TAG production during conditions optimal for growth. Land plants also synthesize TAGs during stresses and we will compare new findings on environmental stress-induced TAG accumulation in plants and microalgae especially in the well-characterized model alga Chlamydomonas reinhardtii and a biotechnologically relevant genus Nannochloropsis.

  5. Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors

    DEFF Research Database (Denmark)

    Poulsen, L K; Stahl Skov, P; Mosbech, H

    1988-01-01

    by a phorbol ester TPA, although not up to the level of anti-IgE. The cells from the high responding donor and a monoclonal anti-IgG4 were selected for further studies. Serum pools from patients allergic to house dust mite (Dermatophagoides pteronyssinus) were used for passive sensitization. The pools...

  6. Induced accumulation of 20-hydroxyecdysone in cell suspension ...

    African Journals Online (AJOL)

    This study describes the effects of culture medium, culture temperature, sucrose concentration and cholesterol feeding on cell growth and 20-hydroxyecdysone production in suspension cultures of Vitex glabrata, an important medicinal plant in Thailand. Cell growth and 20-hydroxyecdysone production were not significantly ...

  7. Induced accumulation of 20-hydroxyecdysone in cell suspension ...

    African Journals Online (AJOL)

    Administrator

    2011-09-12

    Sep 12, 2011 ... This study describes the effects of culture medium, culture temperature, sucrose concentration and cholesterol feeding on cell growth and 20-hydroxyecdysone production in suspension cultures of Vitex glabrata, an important medicinal plant in Thailand. Cell growth and 20-hydroxyecdysone production.

  8. Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4).

    Science.gov (United States)

    Usui, Takuya; Nakazawa, Ayumi; Okura, Takashi; Deguchi, Yoshiharu; Akanuma, Shin-Ichi; Kubo, Yoshiyuki; Hosoya, Ken-Ichi

    2016-11-01

    The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF across the blood-brain barrier and blood-CSF barrier (BCSFB) was investigated using Wistar rats, which were anesthetized with pentobarbital sodium. An in vivo intracerebral microinjection study suggested that there was only partial efflux of [ 3 H]histamine from the rat brain across the blood-brain barrier. The [ 3 H]histamine elimination clearance from the rat CSF was 3.8-fold greater than that of a CSF bulk flow marker, and the elimination of [ 3 H]histamine was significantly inhibited by the co-administration of unlabeled histamine, suggesting the involvement of a carrier-mediated process in histamine elimination from the CSF. The uptake study of [ 3 H]histamine by the isolated rat choroid plexus revealed histamine elimination from the CSF across the BCSFB. The [ 3 H]histamine uptake by TR-CSFB3 cells, a model cell line for the BCSFB, exhibited temperature-dependent and saturable kinetics, suggesting the involvement of carrier-mediated transport of histamine at the BCSFB. In the inhibition study, [ 3 H]histamine uptake by TR-CSFB3 cells was significantly inhibited by substrates and/or inhibitors of plasma membrane monoamine transporter (PMAT/SLC29A4), but not affected by substrates of organic cation transporters. These results suggest the elimination of histamine from the CSF via plasma membrane monoamine transporter at the BCSFB. © 2016 International Society for Neurochemistry.

  9. Histamine protects bone marrow against cellular damage induced by ionising radiation.

    Science.gov (United States)

    Medina, Vanina A; Croci, Máximo; Carabajal, Eliana; Bergoc, Rosa M; Rivera, Elena S

    2010-04-01

    Based on our previous data on the histamine radioprotective effect on small intestine, in the present work we aimed to determine whether histamine is able to protect bone marrow cells against ionising radiation damage. 56 mice and 40 rats were divided into four groups. Histamine and histamine-irradiated groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose on whole-body using Cesium-137 source and were sacrificed three days after irradiation. We evaluated the number of medullar components, bone marrow trophism, oedema, vascular damage, and other histological characteristics and also proliferation markers by immunohistochemistry. Histamine treatment substantially reduced the grade of aplasia, the oedema and vascular damage induced by ionising radiation on bone marrow of mice and rats. Additionally, histamine preserved medullar components increasing the number of megakaryocytes (14.0 +/- 1.0 vs. 7.3 +/- 1.0 in mice; and 9.9 +/- 1.3 vs. 4.1 +/- 1.0 in rats, P effect was associated with an increased proliferation rate of bone marrow cells. Histamine reduces ionising radiation toxicity on bone marrow cells being a suitable candidate for use as radioprotector, especially for patients undergoing radiotherapy who are at the risk of bone marrow or small intestine damage.

  10. Amiodarone increases the accumulation of DEA in a human alveolar epithelium-derived cell line.

    Science.gov (United States)

    Seki, Satoru; Itagaki, Shirou; Kobayashi, Masaki; Hirano, Takeshi; Iseki, Ken

    2008-07-01

    Amiodarone (AMD)-induced pulmonary toxicity (AIPT) is the most life-threatening side-effect of AMD treatment. N-Monodesethylamiodarone (DEA), an active metabolite of AMD, also exhibits cytotoxicity and tends to accumulate in the lung more intensively than AMD. In this study, we characterized the mechanism of DEA accumulation using A549 cells as a model of the alveolar epithelium. Typical ATP-depletion compounds caused an approximately 30% increase in the accumulation of DEA in A549 cells, although these effects were less than those in Caco-2 cells. Triiodothyronine (T(3)), which exhibited an inhibitory effect on DEA efflux in Caco-2 cells, did not affect the accumulation of DEA in A549 cells. On the other hand, 100 microM AMD caused an approximately 200% increase in DEA content in A549 cells, although AMD accumulation was not affected by 100 microM DEA. Since the reducing effect of AMD on cellular ATP levels and that of FCCP were similar, the mechanism by which DEA accumulation is increased by AMD might be different from the ATP-dependent DEA efflux mechanism. The decrease in cell viability by DEA in the presence of AMD (IC(50) value of DEA for A549 cell viability: 25.4+/-2.4 microM) was more pronounced than that by DEA alone (IC(50) value: 11.5+/-3.0 microM). This further DEA accumulation by AMD might be a factor responsible for the greater accumulation of DEA than that of AMD in the lung in long-term AMD-treated patients.

  11. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model

    Science.gov (United States)

    Gschwandtner, M; Mildner, M; Mlitz, V; Gruber, F; Eckhart, L; Werfel, T; Gutzmer, R; Elias, P M; Tschachler, E

    2013-01-01

    Background Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. Methods Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation-associated genes and epidermal junction proteins was quantified by real-time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule. Results The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation-associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls. Conclusions Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases. PMID:23157658

  12. Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity.

    Science.gov (United States)

    Wei, Hong; Jin, Cong-Yu; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2014-12-01

    Among brain structures receiving efferent projections from the histaminergic tuberomammillary nucleus is the pontine locus coeruleus (LC) involved in descending noradrenergic control of pain. Here we studied whether histamine in the LC is involved in descending regulation of neuropathic hypersensitivity. Peripheral neuropathy was induced by unilateral spinal nerve ligation in the rat with a chronic intracerebral and intrathecal catheter for drug administrations. Mechanical hypersensitivity in the injured limb was assessed by monofilaments. Heat nociception was assessed by determining radiant heat-induced paw flick. Histamine in the LC produced a dose-related (1-10μg) mechanical antihypersensitivity effect (maximum effect at 15min and duration of effect 30min), without influence on heat nociception. Pretreatment of LC with zolantidine (histamine H2 receptor antagonist), but not with pyrilamine (histamine H1 receptor antagonist), and spinal administration of atipamezole (an α2-adrenoceptor antagonist), prazosine (an α1-adrenoceptor antagonist) or bicuculline (a GABAA receptor antagonist) attenuated the antihypersensitivity effect of histamine. The histamine-induced antihypersensitivity effect was also reduced by pretreatment of LC with fadolmidine, an α2-adrenoceptor agonist inducing autoinhibition of noradrenergic cell bodies. Zolantidine or pyrilamine alone in the LC failed to influence pain behavior, while A-960656 (histamine H3 receptor antagonist) suppressed hypersensitivity. A plausible explanation for these findings is that histamine, due to excitatory action mediated by the histamine H2 receptor on noradrenergic cell bodies, promotes descending spinal α1/2-adrenoceptor-mediated inhibition of neuropathic hypersensitivity. Blocking the autoinhibitory histamine H3 receptor on histaminergic nerve terminals in the LC facilitates release of histamine and thereby, increases descending noradrenergic pain inhibition. Copyright © 2014 Elsevier Ltd. All rights

  13. Dual effect of magnesium on compound 48/80-induced histamine secretion from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Bertelsen, Niels Haldor; Johansen, Torben

    1991-01-01

    The effect of magnesium on the secretory response to compound 48/80 from rat peritoneal mast cells was studied. The decrease in secretion caused by calcium deprivation was enlarged by magnesium. Glucose partially counteracted the decrease caused by calcium deprivation but not the one caused by ma......-secretion coupling. We propose that insufficient supply of Mg2+ to the G-protein during activation by compound 48/80 might cause a suboptimal signal transduction....

  14. Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

    International Nuclear Information System (INIS)

    Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

    2005-01-01

    Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

  15. Daunomycin accumulation and induction of programmed cell death in rat hair follicles

    DEFF Research Database (Denmark)

    Shin, Masashi; Larsson, Lars-Inge; Hougaard, David M.

    2009-01-01

    -positive matrix cells are detectable up to 48 h after injection and exhibit a characteristic granular morphology, which is not observed in saline-injected controls. TUNEL-staining has revealed that DM injection induces programmed cell death (PCD) in rat hair follicles. Cells undergoing PCD are detectable as late...... and in the outer root sheath. Ultrastructural immunocytochemistry has shown the presence of DM-positive cells with two different types of morphology. About half of the immunopositive cells exhibit a morphology typical of classical apoptosis (PCD type 1), whereas the other half show signs of autophagic cell death...... (PCD type 2). Interestingly, little, if any, DM accumulation or apoptosis has been detected in the dermal hair papillae. This may have a bearing on potential regeneration of the hair follicles. Thus, DM accumulates in a characteristic pattern in hair follicles. This accumulation is associated...

  16. Histamine modulates the cellular stress response in yeast.

    Science.gov (United States)

    Delitheos, Basil; Papamichael, Konstantinos; Tiligada, Ekaterini

    2010-04-01

    The cellular stress response is a universal protective reaction to adverse environmental or microenvironmental conditions, such as heat and drugs, associated in part with the highly conserved heat shock proteins (HSPs). Histamine is a key inflammatory mediator derived from L: -histidine that governs vital cellular processes beyond inflammation, while recent evidence implies additional actions in both prokaryotes and eukaryotes. This study explored the possible role of histamine in the heat shock response in yeast, an established experimental model for the pharmacological investigation of the cellular stress response. The response was evaluated by determining growth and viability of post-logarithmic phase grown yeast cultures after heat shock at 53 degrees C for 30 min. Thermal preconditioning at 37 degrees C for 2 h served as a positive control. The effect of histamine was investigated following long-term administration through the post-logarithmic phase of growth or short-term administration for 2 h prior to heat shock. Short-term treatment with 1 mM histamine resulted in de novo protein synthesis-dependent acquisition of thermotolerance, while lower doses or long-term administration of histamine failed to induce the heat-resistant phenotype. Preliminary investigation of HSP104, HSP70 and HSP60 expression by western blotting showed an increase of these proteins after thermal preconditioning. However, a differential HSP and tubulin expression appeared to underlie the response of yeast cells to histamine. In conclusion, histamine was capable of inducing the adaptive phenotype, while the contribution of HSPs and tubulin and the potential implications remain largely elusive.

  17. Increased brain histamine H3 receptor expression during hibernation in golden-mantled ground squirrels

    Directory of Open Access Journals (Sweden)

    Anichtchik Oleg V

    2003-09-01

    Full Text Available Abstract Background Hibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. We have previously shown that the histamine levels increase in the brain during hibernation, as does the ratio between histamine and its first metabolite, suggesting increased histamine turnover during this state. The inhibitory histamine H3 receptor has both auto- and heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H3 receptor expression would clearly indicate an important hibernation-related function for the receptor. Results In this study we show, using in situ hybridization, that histamine H3 receptor mRNA increases in the cortex, caudate nucleus and putamen during hibernation, an increase that is accompanied by elevated receptor binding in the cerebral cortex, globus pallidus and substantia nigra. These results indicate that there is a hibernation-related increase in H3 receptor expression in cortical neurons and in striatopallidal and striatonigral GABAergic neurons. GTP-γ-S binding autoradiography shows that the H3 receptors in the globus pallidus and substantia nigra can be stimulated by histamine throughout the hibernation cycle, suggesting that they are functionally active during hibernation. Conclusions These results show that the histamine H3 receptor gene is one of the few with a transcript that increases during hibernation, indicating an important role for the receptor in regulating this state. Moreover, the receptor is functionally active in the basal ganglia, suggesting a function for it in regulating e.g. dopaminergic transmission

  18. Dicrocoelium dendriticum induces autophagic vacuoles accumulation in human hepatocarcinoma cells.

    Science.gov (United States)

    Pepe, P; Castellano, M; Alfano, S; Della Pepa, M E; Tirino, V; Piemonte, M; Desiderio, V; Zappavigna, S; Galdiero, M; Caraglia, M; Cringoli, G; Rinaldi, L; Galdiero, M

    2015-09-15

    The relationship between Dicrocoelium dendriticum and cancer has been poorly investigated so far, but a large amount of findings suggest that other trematodes can favour cancer in both animals and humans. In this study, the effects of D. dendriticum on cell proliferation, cell death mechanisms and oxidative stress induction were evaluated in hepatocellular carcinoma (HCC) cell lines (HepG2 and HuH7). Results showed that short time exposure to low concentrations of somatic antigens from D. dendriticum caused slight proliferation in both HepG2 and HuH7 cells while high concentrations and long exposure time to extracts from D. dendriticum caused a significant growth inhibition. This effect was, however, not paralleled by apoptosis but it occurred with an about 40% increase of the formation of autophagic vacuoles. In the same experimental conditions, a strong oxidative stress was recorded with an about 100% increase of the intracellular O(2-). These data suggest the occurrence of an escape anti-apoptotic mechanism in HCC cells. In conclusion, these results suggest a role for D. dendriticum in the chronic oxidative stress and in the regulation of transformation processes in HCC warranting additional investigations in this specific area of research. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Change in the dibenzyldimethylammonium accumulation by irradiated Streptococcus cells caused by radiation damage modifiers

    International Nuclear Information System (INIS)

    Fomenko, B.S.; Leont'eva, G.A.

    1975-01-01

    Anoxia, concentrated cell suspension, glutathione (10 -4 -10 -2 M) or low concentrations of cysteine (10 -4 -10 -3 M) exerted a radioprotective effect and suppressed the accumulation of dibenzyldimethylammonium chloride (DDA + ) by γ-irradiated (40 krad) S. faecalis cells. Dilution of the cell suspensions and higher cysteine concentrations (>10 -3 M) increased the effects of irradiation on bacterial accumulation of DDA + and decreased the cell survival. The lethal action of irradiation apparently involves damage to the mechanisms which maintain a normal membrane potential

  20. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection. Copyright © 2013. Published by Elsevier B.V.

  1. Uranium(VI) complexation in cell culture medium: influence of speciation on Normal Rat Kidney (NRK-52E) cell accumulation

    International Nuclear Information System (INIS)

    Carriere, M.; Khodja, H.; Avoscan, L.; Carrot, F.; Gouget, B.

    2005-01-01

    Uranium bioavailability and toxicity are closely linked to the metal's speciation in solution. However in biological fluids or in media classically used for cell culture - and subsequently for in vitro cell exposure -, uranium is rarely present as free-ion since these media contain non-negligible concentrations of potential ligands such as phosphate and bicarbonate but also co-ions such as calcium which can cause U(VI) complexes precipitation. The chemical form of uranium that is internalized in cells and interferes with biological processes is of major concern. Uranium toxicity and accumulation were evaluated in vitro on NRK-52 E cells, model for rat renal proximal tubule. Uranium intracellular accumulation begins after 12 h exposure to 600 μM U(VI); toxicity appears as soon as cells accumulated 25 to 30 mg U/g protein. Modification of uranium speciation in the exposure medium induces great changes in toxicity and cell accumulation. Comparison of toxicity and accumulation results to theoretical uranium speciation, calculated with the J-Chess computer program, shows that free-ion concentration can not explain the total uranium intracellular accumulation. Low molecular weight U(VI) complexes, such as UO 2 (CO 3 ) 3 4- but also UO 2 PO 4 - could be implicated in U(VI) cellular accumulation and toxicity. (orig.)

  2. Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes.

    Science.gov (United States)

    Takahashi, Hideo; Sadamori, Hiroshi; Teshigawara, Kiyoshi; Niwa, Atsuko; Liu, Keyue; Wake, Hidenori; Mori, Shuji; Yoshino, Tadashi; Nishibori, Masahiro

    2013-10-15

    Cell-cell interaction through binding of adhesion molecules on monocytes to their ligands on T-cells plays roles in cytokine production and lymphocyte proliferation. High mobility group box 1 (HMGB1), an abundant and conserved nuclear protein, acts in the extracellular environment as a primary pro-inflammatory signal. HMGB1 induces expression of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes, resulting in production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). Histamine inhibits pro-inflammatory cytokine production via histamine H2-receptors; however, it is not known whether histamine inhibits HMGB1 activity. This study was designed to study the inhibitory effect of histamine on HMGB1 activity. We examined the effect of histamine on HMGB1-induced expression of ICAM-1, B7.1, B7.2 and CD40 on monocytes, production of IFN-γ and TNF-α and lymphocyte proliferation in PBMCs. Histamine inhibited HMGB1 activity in a concentration-dependent manner. The effects of histamine were partially ablated by the H2-receptor antagonist, famotidine, and mimicked by the H2/H4-receptor agonists, dimaprit and 4-methylhistamine. Histamine induced cyclic adenosine monophosphate (cAMP) production in the presence and absence of HMGB1. The effects of histamine were reversed by the protein kinase A (PKA) inhibitor, H89, and mimicked by the membrane-permeable cAMP analog, dibutyryl cAMP (dbcAMP), and the adenylate cyclase activator, forskolin. These results together indicated that histamine inhibited HMGB1 activity. © 2013 Elsevier B.V. All rights reserved.

  3. A feedback mechanism controlling SCRAMBLED receptor accumulation and cell-type pattern in Arabidopsis.

    Science.gov (United States)

    Kwak, Su-Hwan; Schiefelbein, John

    2008-12-23

    Cellular pattern formation in the root epidermis of Arabidopsis occurs in a position-dependent manner, generating root-hair (H) cells contacting two underlying cortical cells and nonhair (N) cells contacting one cortical cell. SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase (LRR-RLK), mediates this process through its effect on a downstream transcription factor regulatory network. After perception of a positional cue, the SCM signaling pathway is proposed to preferentially repress WEREWOLF (WER) transcription factor expression in H cells and thereby bias the outcome of mutual lateral inhibition acting between H and N cells. However, the molecular mechanism responsible for this preferential SCM signaling is unknown. Here, we analyze the distribution of the SCM receptor and the biological effect of altering its accumulation pattern. We find that SCM expression and accumulation in the epidermal cell layer is necessary and sufficient to direct the cell-type pattern. Further, SCM preferentially accumulates in H cells, and this accumulation pattern is dependent on the downstream transcription factors. Thus, SCM participates in an autoregulatory feedback loop, enabling cells engaged in SCM signaling to maintain high levels of SCM receptor, which provides a simple mechanism for reinforcing a bias in receptor-mediated signaling to ensure robust pattern formation.

  4. ALG-2 knockdown in HeLa cells results in G2/M cell cycle phase accumulation and cell death

    DEFF Research Database (Denmark)

    Høj, Berit Rahbek; la Cour, Peter Jonas Marstrand; Mollerup, Jens

    2009-01-01

    downregulation induces accumulation of HeLa cells in the G2/M cell cycle phase and increases the amount of early apoptotic and dead cells. Caspase inhibition by the pan-caspase inhibitor zVAD-fmk attenuated the increase in the amount of dead cells following ALG-2 downregulation. Thus, our results indicate...... that ALG-2 has an anti-apoptotic function in HeLa cells by facilitating the passage through checkpoints in the G2/M cell cycle phase.......ALG-2 (apoptosis-linked gene-2 encoded protein) has been shown to be upregulated in a variety of human tumors questioning its previously assumed pro-apoptotic function. The aim of the present study was to obtain insights into the role of ALG-2 in human cancer cells. We show that ALG-2...

  5. Propionate induces cell swelling and K+ accumulation in shark rectal gland

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, G.M.; Ziyadeh, F.N.; Mills, J.W.; Booz, G.W.; Kleinzeller, A. (Mount Desert Island Biological Laboratory, Salsbury Cove, ME (USA))

    1989-08-01

    Small organic anions have been reported to induce cell solute accumulation and swelling. To investigate the mechanism of swelling, we utilized preparations of rectal gland cells from Squalus acanthias incubated in medium containing propionate. Propionate causes cells to swell by diffusing across membranes in its nonionic form, acidifying cell contents, and activating the Na+-H+ antiporter. The Na+-H+ exchange process tends to correct intracellular pH (pHi), and thus it maintains a favorable gradient for propionic acid diffusion and allows propionate to accumulate. Activation of the Na+-H+ antiport also facilitates Na+ entry into the cell and Nai accumulation. At the same time Na+-K+-ATPase activity, unaffected by propionate, replaces Nai with Ki, whereas the K+ leak rate, decreased by propionate, allows Ki to accumulate. As judged by {sup 86}Rb+ efflux, the reduction in K+ leak was not due to propionate-induced cell acidification or reduction in Cli concentration. Despite inducing cell swelling, propionate did not disrupt cell structural elements and F actin distribution along cell membranes.

  6. Propionate induces cell swelling and K+ accumulation in shark rectal gland

    International Nuclear Information System (INIS)

    Feldman, G.M.; Ziyadeh, F.N.; Mills, J.W.; Booz, G.W.; Kleinzeller, A.

    1989-01-01

    Small organic anions have been reported to induce cell solute accumulation and swelling. To investigate the mechanism of swelling, we utilized preparations of rectal gland cells from Squalus acanthias incubated in medium containing propionate. Propionate causes cells to swell by diffusing across membranes in its nonionic form, acidifying cell contents, and activating the Na+-H+ antiporter. The Na+-H+ exchange process tends to correct intracellular pH (pHi), and thus it maintains a favorable gradient for propionic acid diffusion and allows propionate to accumulate. Activation of the Na+-H+ antiport also facilitates Na+ entry into the cell and Nai accumulation. At the same time Na+-K+-ATPase activity, unaffected by propionate, replaces Nai with Ki, whereas the K+ leak rate, decreased by propionate, allows Ki to accumulate. As judged by 86 Rb+ efflux, the reduction in K+ leak was not due to propionate-induced cell acidification or reduction in Cli concentration. Despite inducing cell swelling, propionate did not disrupt cell structural elements and F actin distribution along cell membranes

  7. Histamine H4 receptor antagonists: the new antihistamines?

    Science.gov (United States)

    Fung-Leung, Wai-Ping; Thurmond, Robin L; Ling, Ping; Karlsson, Lars

    2004-11-01

    Antihistamines (histamine H1 receptor antagonists) are a mainstay treatment for atopic allergy, yet they are only partially effective in relieving the symptoms of the disease. They also have very limited value for the treatment of asthma, despite the well-characterized bronchoconstrictory effects of histamine. The recent discovery of a fourth histamine receptor (H4), and the realization that it is exclusively expressed on hematopoietic cell types that are most implicated in the development and symptomatology of allergy and asthma, suggests that pharmacological targeting of the H4 receptor, either alone or in combination with H1 receptor antagonists, may prove useful for treating both allergy and asthma. Here we review the known biology associated with the H4 receptor, as well the effects of a highly selective H1 receptor antagonist.

  8. Cell engineering of Escherichia coli allows high cell density accumulation without fed-batch process control.

    Science.gov (United States)

    Bäcklund, Emma; Markland, Katrin; Larsson, Gen

    2008-01-01

    A set of mutations in the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) was used to create Escherichia coli strains with a reduced uptake rate of glucose. This allows a growth restriction, which is controlled on cellular rather than reactor level, which is typical of the fed-batch cultivation concept. Batch growth of the engineered strains resulted in cell accumulation profiles corresponding to a growth rate of 0.78, 0.38 and 0.25 h(-1), respectively. The performance of the mutants in batch cultivation was compared to fed-batch cultivation of the wild type cell using restricted glucose feed to arrive at the corresponding growth profiles. Results show that the acetate production, oxygen consumption and product formation were similar, when a recombinant product was induced from the lacUV5 promoter. Ten times more cells could be produced in batch cultivation using the mutants without the growth detrimental production of acetic acid. This allows high cell density production without the establishment of elaborate fed-batch control equipment. The technique is suggested as a versatile tool in high throughput multiparallel protein production but also for increasing the number of experiments performed during process development while keeping conditions similar to the large-scale fed-batch performance.

  9. Accumulation of invariant NKT cells into inflamed skin in a novel murine model of nickel allergy.

    Science.gov (United States)

    Eguchi, Takanori; Kumagai, Kenichi; Kobayashi, Hiroshi; Shigematsu, Hiroaki; Kitaura, Kazutaka; Suzuki, Satsuki; Horikawa, Tatsuya; Hamada, Yoshiki; Ogasawara, Kouetsu; Suzuki, Ryuji

    2013-01-01

    Nickel (Ni) can cause delayed-type hypersensitivity reactions, which are thought to be mediated by the accumulation of T cells into inflamed skin. Accumulated T cells at the developmental stages in metal allergy are poorly characterized because a suitable animal model has not been established. To investigate the accumulated T cells in allergic inflamed skin, we generated a novel murine model of Ni-induced allergy. The murine model of Ni allergy was induced by two sensitizations of Ni plus lipopolysaccharide solution into the groin followed by three challenges with Ni solution into the footpad. Here we show that a specific TCR repertoire bearing Vα14Jα18, called natural killer (NK) T cells, was expanded monoclonally in BALB/c or C57BL/6 mice. Accumulation of NKT cells was characterized as CD4(+) or CD4(-)CD8(-) T cells. These results suggested that NKT cells are major pathogenic T cells at the elicitation phase of Ni allergy. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Development of a sensitive radioassay of histamine for in vitro allergy testing

    International Nuclear Information System (INIS)

    Faraj, B.A.; Gottieb, G.R.; Camp, V.M.; Kutner, M.; Lolies, P.

    1984-01-01

    A radioenzymatic assay for the measurement of histamine is described, based on the incubation of histamine in the presence of histamine-N-methyl-transferase from rat kidney and [ 3 H-methyl]-S-adenosyl-L-methionine (sp act 15 Ci/mmol) in phosphate buffer, 0.05 mole/l, pH 7.9, at 37 0 C for 60 min. The N-[ 3 H-methyl]histamine generated was selectively extracted into toluene/isoamyl alcohol (3:2) and the quantity of the tritium in the sample was determined by liquid-scintillation counting. As little as 1 nmol/l of histamine can be detected. The assay is specific, with no cross-reactivity noted for several compounds closely related to histamine. The assay was used to measure the released histamine of a group of allergic subjects following the incubation of their blood with various allergens. A good correlation was found between histamine release from whole blood and the response of skin mast cells to intradermal antigen administration

  11. The effect of lead exposure on tracheal responsiveness to methacholine and ovalbumin, total and differential white blood cells count, and serum levels of immunoglobulin E, histamine, and cytokines in guinea pigs.

    Science.gov (United States)

    Farkhondeh, T; Boskabady, M H; Jalali, S; Bayrami, G

    2014-03-01

    The effect of exposure to inhaled lead acetate in guinea pigs was evaluated. The present study comprised of five groups of guinea pigs including control (C), sensitized to ovalbumin (OA; S) and three groups exposed to 0.1, 0.2, and 0.4 M inhaled lead (Pb; n = 6 for each group). Tracheal responsiveness to methacholine and OA, total and differential white blood cells (WBCs) count in lung lavage, serum levels of cytokines (interferon γ (IFN-γ) and interleukin 4 (IL-4)), histamines, and immunoglobulin E (IgE), and Pb concentration in lung were measured. Tracheal responsiveness to methacholine, OA, total and differential WBC types as well as IL-4, IFN-γ, histamine, and IgE were significantly increased but IFN-γ/IL-4 were significantly decreased in sensitized animals as well as those exposed to high Pb concentrations when compared with the control group (from p < 0.05 to p < 0.001). In addition, there was not a significant difference in most measured values between animals exposed to high Pb concentration and group S. The Pb concentration in lung tissues of animals exposed to all three Pb concentrations was significantly higher than that of group C (p < 0.001 for all cases).These results showed that inhaled lead acetate exposure can induce lung inflammatory changes similar to sensitized animals. Therefore, exposure to environmental Pb pollution may cause asthma-like changes.

  12. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal

    Directory of Open Access Journals (Sweden)

    Dhanya N

    2008-01-01

    Full Text Available Background : Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. Aim: To compare the efficacy of levocetirizine (H 1 blocker versus levocetirizine and ranitidine (H 2 blocker in suppressing histamine-induced wheal. Methods: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. Results: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. Conclusion: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.

  13. Accumulation and biological effects of gallium in malignant cell lines in vitro

    International Nuclear Information System (INIS)

    Awano, Takayuki; Matsuzawa, Taiju

    1977-01-01

    Accumulation and biological effects of gallium (Ga) in malignant cells in vitro were studied. Biological effects were investigated cytokinetically and morphologically. The malignant cultured FM3A cells (originated from mammary carcinoma of C3H mice) accumulated 67 Ga actively. This accumulation was more intensive in proliferating cells than in non-proliferating cells. 6.5 percent of 67 Ga accumulated in the cultured FM3A cells was bound loosely at the cell surface. The colony forming capacity of C2W cells (originated from amelanotic melanoma of C57 Black mice ) was studied. The capacity decreased markedly when stable Ga was added to the medium in low concentration, but it decreased very little more in the range of rather high concentration. The growth response of FM3A cells to various concentrations of stable Ga was studied. The saturation density decreased and the doubling time became prolonged with increased Ga concentration. When 0.5 mM of stable Ga was added to the medium, the speed of proliferation changed markedly. The doubling time increased 1.7 times as compared to that before addition of Ga. The shape of the FM3A cells was usually spheroid in the medium. Swelling of the cells was observed when stable Ga was added to the culture medium. In particular, several per cent of these cells showed remarkable changes; that is, the cells were flattened and adhered to the dish and showed remarkable locomotion. It may be that these results are related to cell differentiation rather than to the cytotoxicity of stable Ga. (auth.)

  14. The effect of tanespimycin (17-AAG) on radioiodine accumulation in sodium iodide symporter expressing cells

    International Nuclear Information System (INIS)

    Yu, Kyoung Hyun; Youn, Hyewon; Song, Myung Geun; Lee, Dong Soo; Chung, June Key

    2012-01-01

    The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide sym porter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes. Cells were incubated with tanespimycin in order to evaluate 125 I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT PCR were performed to measure the level of gene expression. After tanespimycin treatment, 125 uptake was in creased by ∼2.5 fold in FRTL 5, hNIS ARO. and hNIS MDA MB 231 cells, but no changes were detected in the hNIS HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL 5 cell. in the FRTL 5 and hNIS ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimtycin treatment was an observed increase in the h hNIS ARO cells. These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the 125I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression

  15. Influence of nimodipine, verapamil and lanthanum on histamine release from human basophils

    DEFF Research Database (Denmark)

    Jensen, C B; Thastrup, Ole; Norn, S

    1987-01-01

    Our previous studies suggest that the membrane content of sialic acid influences histamine release from human basophils by interfering with the transmembraneous calcium fluxes preceding histamine release. In this study we investigated a possible interaction between membrane sialic acid...... and the calcium channels, using the calcium antagonists nimodipine, verapamil and lanthanum. Anti-IgE-induced histamine release was inhibited by verapamil, nimodipine and lanthanum. When cells were pretreated with sialidase in order to remove sialic acid from the cell membrane, the inhibitory action of nimodipine...

  16. Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation

    Science.gov (United States)

    Wang, Lei; Fan, Jia; Hitron, John Andrew; Son, Young-Ok; Wise, James T.F.; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Shi, Xianglin

    2016-01-01

    Nickel compounds are known as human carcinogens. Chronic environmental exposure to nickel is a worldwide health concern. Although the mechanisms of nickel-induced carcinogenesis are not well understood, recent studies suggest that stem cells/cancer stem cells are likely important targets. This study examines the role of cancer stem cells in nickel-induced cell transformation. The nontransformed human bronchial epithelial cell line (Beas-2B) was chronically exposed to nickel chloride for 12 months to induce cell transformation. Nickel induced Beas-2B cell transformation, and cancer stem-like cells were enriched in nickel-transformed cell (BNiT) population. The BNiT cancer stem-like cells demonstrated enhanced self-renewal and distinctive differentiation properties. In vivo tumorigenesis studies show that BNiT cancer stem-like cells possess a high tumor-initiating capability. It was also demonstrated that superoxide dismutase 1 was involved in the accumulation of cancer stem-like cells; the regulation of superoxide dismutase 1 expression was different in transformed stem-like cells and nontransformed. Overall, the accumulation of stem-like cells and their enhanced stemness functions contribute to nickel-induced tumorigenesis. Our study provides additional insight into the mechanisms by which metals or other chemicals can induce carcinogenesis. PMID:26962057

  17. Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability

    International Nuclear Information System (INIS)

    Anghileri, L.J.; Crone-Escanye, M.C.; Thouvenot, P.; Brunotte, F.; Robert, J.

    1988-01-01

    The effects of citrate ion on in vitro and in vivo uptake of [ 67 Ga]citrate by tumor cells have been studied. Carrier-free [ 67 Ga]citrate seems to follow the physical diffusion of citrate ions into the cell, and the presence of carrier gallium inhibits that diffusion, reducing considerably its uptake. These results appear to support the hypothesis that increased permeability of tumor cells is the principal cause of [ 67 Ga]citrate accumulation by tumors

  18. Histamine production by Enterobacter aerogenes in chub mackerel (Scomber japonicus at various storage temperatures

    Directory of Open Access Journals (Sweden)

    Yu ZOU

    Full Text Available Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus were investigated through measuring bacterial count, histidine decarboxylase (HDC activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U/g at 37 °C. Meanwhile, fish samples stored at 25 and 37 °C for 18 h, formed histamine at above 50 mg/100 g of the potential hazard level. In contrast, bacterial growth and histamine formation were controlled for 36 h by cold storage at low temperature (4 °C. Therefore, strict temperature control was necessary for preservation and processing of chub mackerel in order to assure this marine fish safety.

  19. Histamine production by Enterobacter aerogenes in chub mackerel (Scomber japonicus at various storage temperatures

    Directory of Open Access Journals (Sweden)

    Yu ZOU

    2016-01-01

    Full Text Available Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus were investigated through measuring bacterial count, histidine decarboxylase (HDC activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U/g at 37 °C. Meanwhile, fish samples stored at 25 and 37 °C for 18 h, formed histamine at above 50 mg/100 g of the potential hazard level. In contrast, bacterial growth and histamine formation were controlled for 36 h by cold storage at low temperature (4 °C. Therefore, strict temperature control was necessary for preservation and processing of chub mackerel in order to assure this marine fish safety.

  20. Accumulation of Poly(3-hydroxybutyrate Helps Bacterial Cells to Survive Freezing.

    Directory of Open Access Journals (Sweden)

    Stanislav Obruca

    Full Text Available Accumulation of polyhydroxybutyrate (PHB seems to be a common metabolic strategy adopted by many bacteria to cope with cold environments. This work aimed at evaluating and understanding the cryoprotective effect of PHB. At first a monomer of PHB, 3-hydroxybutyrate, was identified as a potent cryoprotectant capable of protecting model enzyme (lipase, yeast (Saccharomyces cerevisiae and bacterial cells (Cupriavidus necator against the adverse effects of freezing-thawing cycles. Further, the viability of the frozen-thawed PHB accumulating strain of C. necator was compared to that of the PHB non-accumulating mutant. The presence of PHB granules in cells was revealed to be a significant advantage during freezing. This might be attributed to the higher intracellular level of 3-hydroxybutyrate in PHB accumulating cells (due to the action of parallel PHB synthesis and degradation, the so-called PHB cycle, but the cryoprotective effect of PHB granules seems to be more complex. Since intracellular PHB granules retain highly flexible properties even at extremely low temperatures (observed by cryo-SEM, it can be expected that PHB granules protect cells against injury from extracellular ice. Finally, thermal analysis indicates that PHB-containing cells exhibit a higher rate of transmembrane water transport, which protects cells against the formation of intracellular ice which usually has fatal consequences.

  1. Accumulation of Poly(3-hydroxybutyrate) Helps Bacterial Cells to Survive Freezing

    Science.gov (United States)

    Krzyzanek, Vladislav; Mravec, Filip; Hrubanova, Kamila; Samek, Ota; Kucera, Dan; Benesova, Pavla; Marova, Ivana

    2016-01-01

    Accumulation of polyhydroxybutyrate (PHB) seems to be a common metabolic strategy adopted by many bacteria to cope with cold environments. This work aimed at evaluating and understanding the cryoprotective effect of PHB. At first a monomer of PHB, 3-hydroxybutyrate, was identified as a potent cryoprotectant capable of protecting model enzyme (lipase), yeast (Saccharomyces cerevisiae) and bacterial cells (Cupriavidus necator) against the adverse effects of freezing-thawing cycles. Further, the viability of the frozen–thawed PHB accumulating strain of C. necator was compared to that of the PHB non-accumulating mutant. The presence of PHB granules in cells was revealed to be a significant advantage during freezing. This might be attributed to the higher intracellular level of 3-hydroxybutyrate in PHB accumulating cells (due to the action of parallel PHB synthesis and degradation, the so-called PHB cycle), but the cryoprotective effect of PHB granules seems to be more complex. Since intracellular PHB granules retain highly flexible properties even at extremely low temperatures (observed by cryo-SEM), it can be expected that PHB granules protect cells against injury from extracellular ice. Finally, thermal analysis indicates that PHB-containing cells exhibit a higher rate of transmembrane water transport, which protects cells against the formation of intracellular ice which usually has fatal consequences. PMID:27315285

  2. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

    Science.gov (United States)

    Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.

    2015-01-01

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K+ (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K+ current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASKf/f mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30–50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30–50 Hz activity in ChAT-Cre:TASKf/f mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. SIGNIFICANCE STATEMENT Attentive states and cognitive function are associated with the generation of γ EEG activity

  3. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

    Science.gov (United States)

    Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

    2015-10-07

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

  4. Comparison of methods for intestinal histamine application

    DEFF Research Database (Denmark)

    Vind, S; Søondergaard, I; Poulsen, L K

    1991-01-01

    The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast ...... conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.......The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast...... all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We...

  5. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    Science.gov (United States)

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea. © 2016 International Society for Neurochemistry.

  6. ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Yoon-hee eHong

    2015-07-01

    Full Text Available Unfolded protein response (UPR is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC, on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively. PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM, apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3 in response to ROS accumulation induced by PEITC (5 µM. ROS scavenger, N-acetyl-cysteine (NAC, attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78, suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.

  7. Potassium accumulation between type I hair cells and calyx terminals in mouse crista.

    Science.gov (United States)

    Lim, Rebecca; Kindig, Angela E; Donne, Scott W; Callister, Robert J; Brichta, Alan M

    2011-05-01

    The mode of synaptic transmission in the vestibular periphery, between type I hair cells and their associated calyx terminal, has been the subject of much debate. The close and extensive apposition of pre- and post-synaptic elements has led some to suggest potassium (K(+)) accumulates in the intercellular space and even plays a role in synaptic transmission. During patch clamp recordings from isolated and embedded hair cells in a semi-intact preparation of the mouse cristae, we noted marked differences in whole-cell currents. Embedded type I hair cells show a prominent droop during steady-state activation as well as a dramatic collapse in tail currents. Responses to a depolarizing voltage step (-124 to +16 mV) in embedded, but not isolated, hair cells resulted in a >40 mV shift of the K(+) equilibrium potential and a rise in effective K(+) concentration (>50 mM) in the intercellular space. Together these data suggest K(+) accumulation in the intercellular space accounts for the different responses in isolated and embedded type I hair cells. To test this notion, we exposed the preparation to hyperosmotic solutions to enlarge the intercellular space. As predicted, the K(+) accumulation effects were reduced; however, a fit of our data with a classic diffusion model suggested K(+) permeability, rather than the intercellular space, had been altered by the hyperosmotic change. These results support the notion that under depolarizing conditions substantial K(+) accumulation occurs in the space between type I hair cells and calyx. The extent of K(+) accumulation during normal synaptic transmission, however, remains to be determined.

  8. The effect of hormones on anthocyanin accumulation in cell cultures of Haplopappus gracilis.

    Science.gov (United States)

    Constabel, F; Shyluk, J P; Gamborg, O L

    1971-12-01

    Suspension cultures of Haplopappus gracilis accumulated anthocyanin when grown in defined media with 4.5×10(-6)M 2,4-D. Transfer of cells to media with 10(-5)M kinetin or benzyladenine and no auxin or 10(-7)M NAA for 6 days resulted in increased anthocyanin concentration of the cells but the total amount of pigment was unaffected due to differences in growth rates. The cultures yielded up to 35 mg pigment per gram dry weight.Cells grown in batch culture in media with 10(-5)M kinetin and with 10(-7) M NAA or 5×10(-5)M NAA sampled and analyzed daily grew at the same rate. The concentration of anthocyanin differed, being lower in cells at 5×10(-5)M NAA. After 6 days there was a rapid increase in pigment formation, and by 14 days the concentration of anthocyanin in cells in the two media were the same.When the cells were cultured in 3.5-1 phytostats and 600 ml culture was replaced daily with 600 ml medium, anthocyanins accumulated when the NAA concentration was 10(-7)M but not at 10(-6)M. At 10(-7)M NAA the cultures remained pigmented and anthocyanin accumulation could be restored after a temporary loss of pigmentation due to an earlier, higher auxin concentration. The changes in concentration of phenylalanine ammonia-lyase did not correspond to changes in the rate of anthocyanin accumulation. The enzyme showed a maximum 4-8 h after inoculation of cells to fresh media. Cells grown on agar plates and rich in anthocyanin were observed to divide without loss of pigmentation, demonstrating that cells differentiated with respect to anthocyanin production undergo mitosis.

  9. Inhibitory effect of bacteriocin-producing lactic acid bacteria against histamine-forming bacteria isolated from Myeolchi-jeot

    Directory of Open Access Journals (Sweden)

    Eun-Seo Lim

    2016-12-01

    Full Text Available Abstract The objectives of this study were to identify the histamine-forming bacteria and bacteriocin- producing lactic acid bacteria (LAB isolated from Myeolchi-jeot according to sequence analysis of the 16S rRNA gene, to evaluate the inhibitory effects of the bacteriocin on the growth and histamine accumulation of histamine-forming bacteria, and to assess the physico-chemical properties of the bacteriocin. Based on 16S rRNA gene sequences, histamine-forming bacteria were identified as Bacillus licheniformis MCH01, Serratia marcescens MCH02, Staphylococcus xylosus MCH03, Aeromonas hydrophila MCH04, and Morganella morganii MCH05. The five LAB strains identified as Pediococcus acidilactici MCL11, Leuconostoc mesenteroides MCL12, Enterococcus faecium MCL13, Lactobacillus sakei MCL14, and Lactobacillus acidophilus MCL15 were found to produce an antibacterial compound with inhibitory activity against the tested histamine-producing bacteria. The inhibitory activity of these bacteriocins obtained from the five LAB remained stable after incubation at pH 4.0–8.0 and heating for 10 min at 80 °C; however, the bacteriocin activity was destroyed after treatment with papain, pepsin, proteinase K, α-chymotrypsin, or trypsin. Meanwhile, these bacteriocins produced by the tested LAB strains also exhibited histamine-degradation ability. Therefore, these antimicrobial substances may play a role in inhibiting histamine formation in the fermented fish products and preventing seafood-related food-borne disease caused by bacterially generated histamine.

  10. Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells.

    Science.gov (United States)

    Notas, George; Nifli, Artemisia-Phoebe; Kampa, Marilena; Pelekanou, Vassiliki; Alexaki, Vasileia-Ismini; Theodoropoulos, Panayiotis; Vercauteren, Joseph; Castanas, Elias

    2012-06-01

    Quercetin is a flavonol modifying a number of cell processes in different cell lines. Here, we present evidence that nonconjugated quercetin enters cells possibly via organic anion transporter polypeptides and quickly accumulates in the nucleus where it concentrates at distinct foci. Furthermore, it induces major transcriptional events with a high number of transcripts being modified over time and about 2200 transcripts being continuously influenced by the agent. The latter transcripts are related to cell cycle and adhesion, xenobiotic metabolism, immune-related factors and transcription. In addition, quercetin up-regulates the expression of estrogen receptors α and β. The overall outcome on cell fate is reflected by an inhibition of cell proliferation, cell cycle arrest in the G1 phase and reduction of the cells' migratory potential due to actin cytoskeleton disorganization. Finally, we report that the flavonol modifies the transcription and/or activity of numerous transcription factors. In conclusion, our data support the idea that quercetin may actively accumulate in discrete cell structures and exert more than just antioxidant actions on epithelial cells by regulating mechanisms related to gene transcription. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

    International Nuclear Information System (INIS)

    Sato, Eisuke; Yamamoto, Tetsuya; Shikano, Naoto; Ogura, Masato; Nakai, Kei; Yoshida, Fumiyo; Uemae, Yoji; Takada, Tomoya; Isobe, Tomonori; Matsumura, Akira

    2014-01-01

    BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0 mM BPA, with 1.0 mM L-Tyr-O-Et and incubating for 60 min. This increase is caused by activation of a system L amino acid exchanger between BPA and L-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation. - Highlights: • We examined optimal L-p-boronophenylalanine (BPA) loading in CHO-K1 cells. • Optimal BPA loading parameters were 1.0 mM and incubation for 60 min. • Intracellular boron accumulation increased upon co-loading BPA with L-Tyr-O-Et. • Optimal L-Tyr-O-Et loading parameters were 1.0 mM and incubation for 60 min. • Co-loading BPA with L-Tyr-O-Et can increase intracellular boron accumulation

  12. Is tyrosine kinase activation involved in basophil histamine release in asthma due to western red cedar?

    Science.gov (United States)

    Frew, A; Chan, H; Salari, H; Chan-Yeung, M

    1998-02-01

    Occupational asthma due to western red cedar is associated with histamine release from basophils and mast cells on exposure to plicatic acid (PA), but the mechanisms underlying this response remain unclear. Specific kinase inhibitors were used to study the role of tyrosine and serine/threonine kinases in PA-induced histamine release from human basophils. Pretreatment with the tyrosine kinase inhibitor methyl 2,5-dihydroxy-cinnamate (MDHC) attenuated histamine release from basophils triggered by anti-IgE (29.8% inhibition; n = 15; P < 0.01) or grass pollen (48% inhibition; n = 6; P < 0.01). Inhibition was concentration-dependent and could be reversed by washing the cells in buffer, while the inactive stereoisomer of MDHC did not affect histamine release. In contrast, the protein kinase C inhibitor staurosporine did not affect histamine release by either anti-IgE or grass pollen. Pretreatment with MDHC partially inhibited PA-induced histamine release from basophils of 6/9 patients with red cedar asthma (25.4% vs 33.8%; P = NS). Staurosporine gave a similar level of inhibition of PA-induced histamine release (25.3% vs 33.8%; P = NS). Thus, signal transduction of the human basophil Fc epsilon RI appears to depend upon tyrosine kinase activation, but not on protein kinase C (serine/threonine kinase) activation. The lack of specific effect on plicatic acid-induced histamine release in basophils obtained from patients with occupational asthma due to western red cedar suggests that tyrosine kinases are not as important in this disease as in atopic asthma, and is consistent with the view that histamine release in red cedar asthma is largely IgE-independent.

  13. Adenovirus type 5 induces progression of quiescent rat cells into S phase without polyamine accumulation.

    Science.gov (United States)

    Cheetham, B F; Shaw, D C; Bellett, A J

    1982-01-01

    Adenovirus type 5 induces cellular DNA synthesis and thymidine kinase in quiescent rat cells but does not induce ornithine decarboxylase. We now show that unlike serum, adenovirus type 5 fails to induce S-adenosylmethionine decarboxylase or polyamine accumulation. The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis. Thus, induction of cellular thymidine kinase and DNA replication by adenovirus type 5 is uncoupled from polyamine accumulation. PMID:7177112

  14. Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population.

    Science.gov (United States)

    Latorre-Moratalla, M L; Comas-Basté, O; Bover-Cid, S; Vidal-Carou, M C

    2017-01-01

    Tyramine and histamine are the main dietary bioactive amines related to acute adverse health effects. Dry fermented sausages can easily accumulate high levels of these hazards and are frequently consumed in Spain. The present work aims to assess the exposure to tyramine and histamine from the consumption of dry fermented sausages by the Spanish population and to assess the risk to suffer acute health effects from this exposure. A probabilistic estimation of the exposure to these hazards was derived combining probability distributions of these amines in dry fermented sausages (n = 474) and their consumption by the Spanish population. The mean dietary exposure to tyramine and histamine was 6.2 and 1.39 mg/meal, respectively. The risk of suffering hypertensive crisis or histamine intoxication by healthy population due to tyramine or histamine intake, respectively, exclusively from dry fermented sausages, can be considered negligible. For individuals under treatment with MAOI drugs, the probability to surpass the safe threshold dose (6 mg/meal) was estimated as 34%. For patients with histamine intolerance, even the presence of this amine in food is not tolerable and it could be estimated that 7000 individuals per million could be at risk to suffer the related symptoms after consuming dry fermented sausages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Histamine-producing Lactobacillus parabuchneri strains isolated from grated cheese can form biofilms on stainless steel.

    Science.gov (United States)

    Diaz, Maria; Del Rio, Beatriz; Sanchez-Llana, Esther; Ladero, Victor; Redruello, Begoña; Fernández, María; Martin, M Cruz; Alvarez, Miguel A

    2016-10-01

    The consumption of food containing large amounts of histamine can lead to histamine poisoning. Cheese is one of the most frequently involved foods. Histamine, one of the biogenic amines (BAs) exhibiting the highest safety risk, accumulates in food contaminated by microorganisms with histidine decarboxylase activity. The origin of these microorganisms may be very diverse with contamination likely occurring during post-ripening processing, but the microorganisms involved during this manufacturing step have never been identified. The present work reports the isolation of 21 histamine-producing Lactobacillus parabuchneri strains from a histamine-containing grated cheese. PCR revealed that every isolate carried the histidine decarboxylase gene (hdcA). Eight lineages were identified based on the results of genome PFGE restriction analysis plus endonuclease restriction profile analysis of the carried plasmids. Members of all lineages were able to form biofilms on polystyrene and stainless steel surfaces. L. parabuchneri is therefore an undesirable species in the dairy industry; the biofilms it can produce on food processing equipment represent a reservoir of histamine-producing bacteria and thus a source of contamination of post-ripening-processed cheeses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Isolation and typification of histamine-producing Lactobacillus vaginalis strains from cheese.

    Science.gov (United States)

    Diaz, Maria; del Rio, Beatriz; Ladero, Victor; Redruello, Begoña; Fernández, María; Martin, Maria Cruz; Alvarez, Miguel A

    2015-12-23

    In food, the biogenic amine (BA) histamine is mainly produced by histidine decarboxylation catalysed by microbial histidine decarboxylase. The consumption of foods containing high concentrations of histamine can trigger adverse neurological, gastrointestinal and respiratory reactions. Indeed, histamine is one of the most toxic of all BAs, and is often detected in high concentration in cheese. However, little is known about the microorganisms responsible for its accumulation in this food. In the present work, 25 histamine-producing Lactobacillus vaginalis strains were isolated from a blue-veined cheese (the first time that histamine-producing strains of this species have been isolated from any food). The restriction profiles of their genomes were analysed by PFGE, and seven lineages identified. The presence of the histidine decarboxylase gene (hdcA) was confirmed by PCR. The nucleotide sequence and genetic organisation of the histamine biosynthesis gene cluster (HDC) and its flanking regions are described for a representative strain (L. vaginalis IPLA11050). Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Accumulation of phenylpropanoid derivatives in chitosan-induced cell suspension culture of Cocos nucifera.

    Science.gov (United States)

    Chakraborty, Moumita; Karun, Anitha; Mitra, Adinpunya

    2009-01-01

    Chitosan-induced elicitation responses of dark-incubated Cocos nucifera (coconut) endosperm cell suspension cultures led to the rapid formation of phenylpropanoid derivatives, which essentially mimics the defense-induced biochemical changes in coconut palm as observed under in vivo conditions. An enhanced accumulation of p-hydroxybenzoic acid as the major wall-bound phenolics was evident. This was followed by p-coumaric acid and ferulic acid. Along with enhanced peroxidases activities in elicited lines, the increase in activities of the early phenylpropanoid pathway enzymes such as, phenylalanine ammonia lyase (PAL), p-coumaroyl-CoA ligase (4CL) and p-hydroxybenzaldehyde dehydrogenase (HBD) in elicited cell cultures were also observed. Furthermore, supplementation of specific inhibitors of PAL, C4H and 4CL in elicited cell cultures led to suppressed accumulation of p-hydroxybenzoic acid, which opens up interesting questions regarding the probable route of the biosynthesis of this phenolic acid in C. nucifera.

  18. Daunorubicin and doxorubicin inhibit the [{sup 11}C]choline accumulation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mikecz, Pal [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary)], E-mail: pal@pet.dote.hu; Marian, Terez; Miklovicz, Tuende; Galuska, Laszlo [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Krasznai, Zoltan; Toth, Agnes; Goda, Katalin [Department of Biophysics and Cell Biology, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Tron, Lajos [Department of Nuclear Medicine, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary); Hernadi, Zoltan; Krasznai, Zoard T. [Department of Obstetrics and Gynecology, University of Debrecen, Medical and Health Science Centre, 4012 Debrecen, Nagyerdei krt. 98 (Hungary)

    2009-10-15

    We studied how very short (10-40 min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [{sup 18}F]FDG and [{sup 11}C]choline was measured. Anthracycline treatment decreased remarkably the [{sup 11}C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [{sup 18}F]FDG uptake of the cells.

  19. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

    1996-01-01

    storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine.......0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33.......0-485.0) nmol/l at day 35 in whole blood, from 18.8 (range 8.2-38.5) to 328.5 (range 224.0-1137.0) nmol/l in plasma-reduced whole blood, and from 0.5 (range 0.5-1.5) to 2.2 (range 1.4-6.9) nmol/l in SAGM blood. These results show spontaneous histamine release during storage of human blood products which contain...

  20. Histamine receptors and antihistamines: from discovery to clinical applications.

    Science.gov (United States)

    Cataldi, Mauro; Borriello, Francesco; Granata, Francescopaolo; Annunziato, Lucio; Marone, Gianni

    2014-01-01

    The synthesis and the identification of histamine marked a milestone in both pharmacological and immunological research. Since Sir Henry Dale and Patrick Laidlaw described some of its physiological effects in vivo in 1910, histamine has been shown to play a key role in the control of gastric acid secretion and in allergic disorders. Using selective agonists and antagonists, as well as molecular biology tools, four histamine receptors (H1R, H2R, H3R and H4R) have been identified. The Nobel Prize in Physiology and Medicine was awarded to Daniel Bovet in 1957 for the discovery of antihistamines (anti-H1R) and to Sir James Black in 1988 for the identification of anti-H2R antagonists. Anti-H1R and anti-H2R histamine receptor antagonists have revolutionized the treatment of certain allergic disorders and gastric acid-related conditions, respectively. More recently, anti-H3R antagonists have entered early-phase clinical trials for possible application in obesity and a variety of neurologic disorders. The preferential expression of H4R by several immune cells and its involvement in the development of allergic inflammation provide the rationale for the use of anti-H4R antagonists in allergic and in other immune-related disorders. © 2014 S. Karger AG, Basel.

  1. Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer.

    OpenAIRE

    Man, W K; Thompson, J N; Baron, J H; Spencer, J

    1986-01-01

    Gastric mucosal concentrations of histamine and of its metabolic enzyme, histamine methyltransferase activity, were measured in patients with duodenal ulcer disease and patients with an apparently normal stomach and duodenum. Patients with duodenal ulcer had significantly less (p less than 0.05) mucosal histamine (median 204 nmol/g) than control subjects (median 252 nmol/g). There was no significant difference between the two groups in their histamine methyltransferase activity values. Omepra...

  2. Regenerative capacity of old muscle stem cells declines without significant accumulation of DNA damage.

    Directory of Open Access Journals (Sweden)

    Wendy Cousin

    Full Text Available The performance of adult stem cells is crucial for tissue homeostasis but their regenerative capacity declines with age, leading to failure of multiple organs. In skeletal muscle this failure is manifested by the loss of functional tissue, the accumulation of fibrosis, and reduced satellite cell-mediated myogenesis in response to injury. While recent studies have shown that changes in the composition of the satellite cell niche are at least in part responsible for the impaired function observed with aging, little is known about the effects of aging on the intrinsic properties of satellite cells. For instance, their ability to repair DNA damage and the effects of a potential accumulation of DNA double strand breaks (DSBs on their regenerative performance remain unclear. This work demonstrates that old muscle stem cells display no significant accumulation of DNA DSBs when compared to those of young, as assayed after cell isolation and in tissue sections, either in uninjured muscle or at multiple time points after injury. Additionally, there is no significant difference in the expression of DNA DSB repair proteins or globally assayed DNA damage response genes, suggesting that not only DNA DSBs, but also other types of DNA damage, do not significantly mark aged muscle stem cells. Satellite cells from DNA DSB-repair-deficient SCID mice do have an unsurprisingly higher level of innate DNA DSBs and a weakened recovery from gamma-radiation-induced DNA damage. Interestingly, they are as myogenic in vitro and in vivo as satellite cells from young wild type mice, suggesting that the inefficiency in DNA DSB repair does not directly correlate with the ability to regenerate muscle after injury. Overall, our findings suggest that a DNA DSB-repair deficiency is unlikely to be a key factor in the decline in muscle regeneration observed upon aging.

  3. Xylella fastidiosa differentially accumulates mineral elements in biofilm and planktonic cells.

    Directory of Open Access Journals (Sweden)

    Paul A Cobine

    Full Text Available Xylella fastidiosa is a bacterial plant pathogen that infects numerous plant hosts. Disease develops when the bacterium colonizes the xylem vessels and forms a biofilm. Inductively coupled plasma optical emission spectroscopy was used to examine the mineral element content of this pathogen in biofilm and planktonic states. Significant accumulations of copper (30-fold, manganese (6-fold, zinc (5-fold, calcium (2-fold and potassium (2-fold in the biofilm compared to planktonic cells were observed. Other mineral elements such as sodium, magnesium and iron did not significantly differ between biofilm and planktonic cells. The distribution of mineral elements in the planktonic cells loosely mirrors the media composition; however the unique mineral element distribution in biofilm suggests specific mechanisms of accumulation from the media. A cell-to-surface attachment assay shows that addition of 50 to 100 µM Cu to standard X. fastidiosa media increases biofilm, while higher concentrations (>200 µM slow cell growth and prevent biofilm formation. Moreover cell-to-surface attachment was blocked by specific chelation of copper. Growth of X. fastidiosa in microfluidic chambers under flow conditions showed that addition of 50 µM Cu to the media accelerated attachment and aggregation, while 400 µM prevented this process. Supplementation of standard media with Mn showed increased biofilm formation and cell-to-cell attachment. In contrast, while the biofilm accumulated Zn, supplementation to the media with this element caused inhibited growth of planktonic cells and impaired biofilm formation. Collectively these data suggest roles for these minerals in attachment and biofilm formation and therefore the virulence of this pathogen.

  4. Xylella fastidiosa differentially accumulates mineral elements in biofilm and planktonic cells.

    Science.gov (United States)

    Cobine, Paul A; Cruz, Luisa F; Navarrete, Fernando; Duncan, Daniel; Tygart, Melissa; De La Fuente, Leonardo

    2013-01-01

    Xylella fastidiosa is a bacterial plant pathogen that infects numerous plant hosts. Disease develops when the bacterium colonizes the xylem vessels and forms a biofilm. Inductively coupled plasma optical emission spectroscopy was used to examine the mineral element content of this pathogen in biofilm and planktonic states. Significant accumulations of copper (30-fold), manganese (6-fold), zinc (5-fold), calcium (2-fold) and potassium (2-fold) in the biofilm compared to planktonic cells were observed. Other mineral elements such as sodium, magnesium and iron did not significantly differ between biofilm and planktonic cells. The distribution of mineral elements in the planktonic cells loosely mirrors the media composition; however the unique mineral element distribution in biofilm suggests specific mechanisms of accumulation from the media. A cell-to-surface attachment assay shows that addition of 50 to 100 µM Cu to standard X. fastidiosa media increases biofilm, while higher concentrations (>200 µM) slow cell growth and prevent biofilm formation. Moreover cell-to-surface attachment was blocked by specific chelation of copper. Growth of X. fastidiosa in microfluidic chambers under flow conditions showed that addition of 50 µM Cu to the media accelerated attachment and aggregation, while 400 µM prevented this process. Supplementation of standard media with Mn showed increased biofilm formation and cell-to-cell attachment. In contrast, while the biofilm accumulated Zn, supplementation to the media with this element caused inhibited growth of planktonic cells and impaired biofilm formation. Collectively these data suggest roles for these minerals in attachment and biofilm formation and therefore the virulence of this pathogen.

  5. Histamine Recycling Is Mediated by CarT, a Carcinine Transporter in Drosophila Photoreceptors

    Science.gov (United States)

    Xu, Ying; An, Futing; Borycz, Jolanta A.; Borycz, Janusz; Meinertzhagen, Ian A.; Wang, Tao

    2015-01-01

    Histamine is an important chemical messenger that regulates multiple physiological processes in both vertebrate and invertebrate animals. Even so, how glial cells and neurons recycle histamine remains to be elucidated. Drosophila photoreceptor neurons use histamine as a neurotransmitter, and the released histamine is recycled through neighboring glia, where it is conjugated to β-alanine to form carcinine. However, how carcinine is then returned to the photoreceptor remains unclear. In an mRNA-seq screen for photoreceptor cell-enriched transporters, we identified CG9317, an SLC22 transporter family protein, and named it CarT (Carcinine Transporter). S2 cells that express CarT are able to take up carcinine in vitro. In the compound eye, CarT is exclusively localized to photoreceptor terminals. Null mutations of cart alter the content of histamine and its metabolites. Moreover, null cart mutants are defective in photoreceptor synaptic transmission and lack phototaxis. These findings reveal that CarT is required for histamine recycling at histaminergic photoreceptors and provide evidence for a CarT-dependent neurotransmitter trafficking pathway between glial cells and photoreceptor terminals. PMID:26713872

  6. Molecular mechanism of intracellular lipid accumulation: Suppressive effect of PycnogenolR in liver cells

    Directory of Open Access Journals (Sweden)

    Shoichiro Ikuyama

    2013-09-01

    Full Text Available ABSTRACTCells are physiologically ready to accumulate lipids such as triacylglycerides in the cytoplasm.Five classes of perilipin (PLIN family proteins are known to be involved in the process of intracellular lipid accumulation. PLIN2 is expressed ubiquitously including adipocytes, hepatocytes and macrophages. Over-expression of PLIN2 is demonstrated in the lesions of fatty liver diseases and atherosclerosis. Suppression of PLIN2 expression prevents from developing these pathological conditions in animal models, suggesting that PLIN2 could be a therapeutic target molecule for excessive intracellular lipid accumulation which leads to various metabolic derangements. The PLIN2 gene promoter has two important cis-acting elements in close proximity:AP-1 element which mediates inflammatory signals and PPRE which mediates free fatty acid effect. In NMuLi mouse liver cells, FFA such as oleic acid requires both functional AP-1 and PPRE simultaneously to stimulate the promoter activity, indicating the presence of intimate interaction of inflammatory and metabolic signals on this gene. PycnogenolR, French maritime pine bark extracts, suppressed the oleic acid-induced PLIN2 expression and lipid accumulation in NMuLi cells. We found that PycnogenolR did not suppress the PLIN2 promoter activity or AP-1 binding to DNA. Instead, PycnogenolRfacilitates the PLIN2 mRNA degradation, leading to suppression of lipid accumulation. This effect seems to be independent of antioxidant effect of PycnogenolR.We raise the idea that PLIN2 is a putative target molecule for prevention of pathological condition induced by excessive lipid accumulation, and this class of natural compounds could be putative therapeutic modalities.Key words: PycnogenolR, lipid droplet, perilipin, fatty liver disease

  7. Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.

    Directory of Open Access Journals (Sweden)

    Jacquelyn Gerhart

    Full Text Available Posterior capsule opacification (PCO is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.

  8. Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.

    Science.gov (United States)

    Koyanagi, Naoto; Imai, Takahiko; Shindo, Keiko; Sato, Ayuko; Fujii, Wataru; Ichinohe, Takeshi; Takemura, Naoki; Kakuta, Shigeru; Uematsu, Satoshi; Kiyono, Hiroshi; Maruzuru, Yuhei; Arii, Jun; Kato, Akihisa; Kawaguchi, Yasushi

    2017-10-02

    Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific CD8+ T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of CD8+ T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.

  9. Factors affecting polyhydroxybutyrate accumulation in mesophyll cells of sugarcane and switchgrass

    Science.gov (United States)

    2014-01-01

    Background Polyhydroxyalkanoates are linear biodegradable polyesters produced by bacteria as a carbon store and used to produce a range of bioplastics. Widespread polyhydroxyalkanoate production in C4 crops would decrease petroleum dependency by producing a renewable supply of biodegradable plastics along with residual biomass that could be converted into biofuels or energy. Increasing yields to commercial levels in biomass crops however remains a challenge. Previously, lower accumulation levels of the short side chain polyhydroxyalkanoate, polyhydroxybutyrate (PHB), were observed in the chloroplasts of mesophyll (M) cells compared to bundle sheath (BS) cells in transgenic maize (Zea mays), sugarcane (Saccharum sp.), and switchgrass (Panicum virgatum L.) leading to a significant decrease in the theoretical yield potential. Here we explore various factors which might affect polymer accumulation in mesophyll cells, including targeting of the PHB pathway enzymes to the mesophyll plastid and their access to substrate. Results The small subunit of Rubisco from pea effectively targeted the PHB biosynthesis enzymes to both M and BS chloroplasts of sugarcane and switchgrass. PHB enzyme activity was retained following targeting to M plastids and was equivalent to that found in the BS plastids. Leaf total fatty acid content was not affected by PHB production. However, when fatty acid synthesis was chemically inhibited, polymer accumulated in M cells. Conclusions In this study, we provide evidence that access to substrate and neither poor targeting nor insufficient activity of the PHB biosynthetic enzymes may be the limiting factor for polymer production in mesophyll chloroplasts of C4 plants. PMID:25209261

  10. Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.

    Science.gov (United States)

    Ishida, Takashi; Suzuki, Sachie; Lai, Chen-Yi; Yamazaki, Satoshi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu; Otsu, Makoto

    2017-04-01

    Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  11. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  12. Proliferative effect of histamine on MA-10 Leydig tumor cells mediated through HRH2 activation, transient elevation in cAMP production, and increased extracellular signal-regulated kinase phosphorylation levels.

    Science.gov (United States)

    Pagotto, Romina María; Monzón, Casandra; Moreno, Marcos Besio; Pignataro, Omar Pedro; Mondillo, Carolina

    2012-06-01

    Mast cells (MC) occur normally in the testis with a species-specific distribution, yet their precise role remains unclear. Testicular MC express histidine decarboxylase (HDC), the unique enzyme responsible for histamine (HA) generation. Evidence to date supports a role for HA as a local regulator of steroidogenesis via functional H₁ and H₂ receptor subtypes (HRH1 and HRH2, respectively) present in Leydig cells. Given that HA is a well-known modulator of physiological and pathological proliferation in many different cell types, we aimed in the present study to evaluate whether HA might contribute to the regulation of Leydig cell number as well as to the control of androgen production. Herein, we demonstrate, to our knowledge for the first time, that MA-10 Leydig tumor cells, but not normal immature Leydig cells (ILC), exhibit a proliferative response upon stimulation with HA that involves HRH2 activation, transient elevation of cAMP levels, and increased extracellular signal-regulated kinase (ERK) phosphorylation. Our results also reveal that MA-10 cells show significantly heightened HDC expression compared to normal ILC or whole-testicular lysate and that inhibition of HDC activity decreases MA-10 cell proliferation, suggesting a possible correlation between autocrine overproduction of HA and abnormally increased proliferation in Leydig cells. The facts that germ cells are also both source and target of HA and that multiple testicular cells are susceptible to HA action underline the importance of the present study, which we hope will serve as a first step for further research into regulation of non-MC-related HDC expression within the testis and its significance for testicular function.

  13. Histamine protects bone marrow against cellular damage induced by Ionizing radiation

    International Nuclear Information System (INIS)

    Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

    2008-01-01

    After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

  14. Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea.

    Science.gov (United States)

    Heinrich, Ulf-Rüdiger; Schmidtmann, Irene; Strieth, Sebastian; Helling, Kai

    2015-08-01

    Intratympanic gentamicin therapy has become a popular treatment modality for Ménière's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detected in every cochlear cell type, but with spatiotemporal variability. One day after application, an intense staining reaction was found in all cell types except the spiral ganglion cells and the stria vascularis. Six days later, gentamicin staining intensities were additionally reduced in the nerve fibers and the spiral ligament. Statistic analysis revealed strong cellular associations in respect to aminoglycoside accumulation. Furthermore, associations with recorded hearing losses were identified comparing the cellular gentamicin content in the organ of Corti, in the stria vascularis, in the spiral ganglion cells and in fibrocytes of the Limbus. In the lateral wall, clear differences in cellular gentamicin accumulation were found between type I fibrocytes of the spiral ligament compared with basal and intermediate cells of the stria vascularis. This finding was unexpected as these three cell types belong to a well-developed gap-junction system which normally enables unhampered cell communication. Cellular differences in local gentamicin storage capacities, transport processes and inherent diffusion barriers are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Lipid accumulation in human breast cancer cells injured by iron depletors.

    Science.gov (United States)

    De Bortoli, Maida; Taverna, Elena; Maffioli, Elisa; Casalini, Patrizia; Crisafi, Francesco; Kumar, Vikas; Caccia, Claudio; Polli, Dario; Tedeschi, Gabriella; Bongarzone, Italia

    2018-04-03

    Current insights into the effects of iron deficiency in tumour cells are not commensurate with the importance of iron in cell metabolism. Studies have predominantly focused on the effects of oxygen or glucose scarcity in tumour cells, while attributing insufficient emphasis to the inadequate supply of iron in hypoxic regions. Cellular responses to iron deficiency and hypoxia are interlinked and may strongly affect tumour metabolism. We examined the morphological, proteomic, and metabolic effects induced by two iron chelators-deferoxamine (DFO) and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT)-on MDA-MB-231 and MDA-MB-157 breast cancer cells. These chelators induced a cytoplasmic massive vacuolation and accumulation of lipid droplets (LDs), eventually followed by implosive, non-autophagic, and non-apoptotic death similar to methuosis. Vacuoles and LDs are generated by expansion of the endoplasmic reticulum (ER) based on extracellular fluid import, which includes unsaturated fatty acids that accumulate in LDs. Typical physiological phenomena associated with hypoxia are observed, such as inhibition of translation, mitochondrial dysfunction, and metabolic remodelling. These survival-oriented changes are associated with a greater expression of epithelial/mesenchymal transcription markers. Iron starvation induces a hypoxia-like program able to scavenge nutrients from the extracellular environment, and cells assume a hypertrophic phenotype. Such survival strategy is accompanied by the ER-dependent massive cytoplasmic vacuolization, mitochondrial dysfunctions, and LD accumulation and then evolves into cell death. LDs containing a greater proportion of unsaturated lipids are released as a consequence of cell death. The consequence of the disruption of iron metabolism in tumour tissue and the effects of LDs on intercellular communication, cancer-inflammation axis, and immunity remain to be explored. Considering the potential benefits, these are crucial

  16. On a accumulation of 131-I-RNase by ascites tumour cells of mice

    International Nuclear Information System (INIS)

    Sarrach, D.; Waldner, H.

    1976-01-01

    The accumulation of 131-I-labelled RNase by Ehrlich ascites tumour cells of mice was investigated in dependence on time, concentration, and pH. Kinetically a fast and a slow stage of reaction is distinguished. In both, the dependence on concentration is of the Langmuir type. Only the stage-I binding is reversibly diminished with increasing pH. Absorption due to electrostatic forces is suggested for this stae. (author)

  17. Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Clara Lehmann

    2010-06-01

    Full Text Available Circulating plasmacytoid dendritic cells (pDC decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha, which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+ T cells, thus playing into the mechanisms of AIDS immunopathogenesis.

  18. [Development of aloin cells and accumulation of anthraquinone in aloe leaf].

    Science.gov (United States)

    Wang, Tai Xia; Li, Jing Yuan; Shen, Zong Gen; Hu, Zheng Hai

    2003-10-01

    The development of aloin cells and its relationship with the accumulation of anthraquinone in aloe leaf were investigated with the methods of paraffin section, semi-thin section, histochemistry and fluorescent microscopy. The results showed: cells rounded the procambium bundle differentiated into bundle sheath at the initial stage of procambium bundle developing into vascular bundle. When the sieve tube members appeared in protophloem, there were a lay of procambium bundle cells reserved between the sieve tube members and bundle sheath. These cells began to devise, then developed into aloin cells through enlargement of volume and vacuolization with the differentiation of metaphloem and metaxylem. So the aloin cells were special phloem parenchyma cells because they shared the same origin with the other phloem cells. The investigation of histochemistry reflected that there were aloin precipitate in the central vacuole of aloin cells after the material was soaked in the liquid of 1% lead acetate [Pb (CH3COO)2]. In addition, the yellow fluorescence was observed in aloin cells when the section of fresh material was investigated under the fluorescent microscope with blue light, which suggested the aloin cells of vascular bundles were the mainly storage site of anthraquinone.

  19. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

    Directory of Open Access Journals (Sweden)

    Yi Eunhee S

    2010-04-01

    Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

  20. Phosphocitrate inhibits mitochondrial and cytosolic accumulation of calcium in kidney cells in vivo.

    Science.gov (United States)

    Tew, W P; Malis, C D; Howard, J E; Lehninger, A L

    1981-01-01

    Synthetic 3-phosphocitrate, an extremely potent inhibitor of calcium phosphate crystallization as determined in a nonbiological physical-chemical assay, has many similarities to a mitochondrial factor that inhibits crystallization of nondiffracting amorphous calcium phosphate. In order to determine whether phosphocitrate can prevent uptake and crystallization of calcium phosphate in mitochondria in vivo, it was administered intraperitoneally to animals given large daily doses of calcium gluconate or parathyroid hormone, a regimen that causes massive accumulation and crystallization of calcium phosphate in the mitochondria and cytosol of renal tubule cells in vivo. Administration of phosphocitrate greatly reduced the net uptake of Ca2+ by the kidneys and prevented the appearance of apatite-like crystalline structures within the mitochondrial matrix and cytosol of renal tubule cells. Phosphocitrate, which is a poor chelator of Ca2+, did not reduce the hypercalcemia induced by either agent. These in vivo observations therefore indicate that phosphocitrate acts primarily at the cellular level to prevent the extensive accumulation of calcium phosphate in kidney cells by inhibiting the mitochondrial accumulation or crystallization of calcium phosphate. Images PMID:6946490

  1. Selected terpenes from leaves of Ocimum basilicum L. induce hemoglobin accumulation in human K562 cells.

    Science.gov (United States)

    Giordana, Feriotto; Nicola, Marchetti; Valentina, Costa; Torricelli, Piera; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

    2018-02-13

    Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for β-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in β-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially, dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin accumulation superior to hydroxyurea and rapamycin and a strongest γ-globin mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A blend of these three terpenes fully replicated the ObEO's biological effect, thus indicating that one of them or all together could be the active ingredients. When terpenes were tested individually, eugenol was the only one inducing stable hemoglobin accumulation, while eucalyptol and linalool produced only a small transient response. However, eugenol potential was strongly enhanced in the presence of eucalyptol and linalool, suggesting a synergistic effect on hemoglobin accumulation. By these results, the discovery of a new inducer and the interesting activity of a blend of major terpenes from ObOE on Hb accumulation could have positive fallouts on β-thalassemia and sickle cells anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Zinc supplementation protects against cadmium accumulation and cytotoxicity in Madin-Darby bovine kidney cells.

    Directory of Open Access Journals (Sweden)

    Ding Zhang

    Full Text Available Cadmium ions (Cd2+ have been reported to accumulate in bovine tissues, although Cd2+ cytotoxicity has not been investigated thoroughly in this species. Zinc ions (Zn2+ have been shown to antagonize the toxic effects of heavy metals such as Cd2+ in some systems. The present study investigated Cd2+ cytotoxicity in Madin-Darby bovine kidney (MDBK epithelial cells, and explored whether this was modified by Zn2+. Exposure to Cd2+ led to a dose- and time-dependent increase in apoptotic cell death, with increased intracellular levels of reactive oxygen species and mitochondrial damage. Zn2+ supplementation alleviated Cd2+-induced cytotoxicity and this protective effect was more obvious when cells were exposed to a lower concentration of Cd2+ (10 μM, as compared to 50 μM Cd2+. This indicated that high levels of Cd2+ accumulation might induce irreversible damage in bovine kidney cells. Metallothioneins (MTs are metal-binding proteins that play an essential role in heavy metal ion detoxification. We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells. Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 μM Cd2+. These findings revealed a protective role of Zn2+ in counteracting Cd2+ uptake and toxicity in MDBK cells, indicating that this approach may provide a means to protect livestock from excessive Cd2+ accumulation.

  3. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia

  4. Dehydropachymic acid decreases bafilomycin A1 induced β-Amyloid accumulation in PC12 cells.

    Science.gov (United States)

    Yu, Mengyao; Xu, Xiaoyan; Jiang, Nan; Wei, Wei; Li, Fang; He, Liming; Luo, Xia

    2017-02-23

    Fuling, the sclerotium of Poria cocos, was frequently used in traditional Chinese medicine (TCM) formulae for Alzheimer's disease (AD) intervention over the past 10 centuries. And its extracts exhibited significant effects in both cellular and animal models of AD in previous studies. However, its mechanisms on prevention and treatment of AD have not been well elucidated yet. To investigate the effect and corresponding mechanisms of dehydropachymic acid, which is one of the major triterpenes in P. cocos, on the clearance of β-amyloid accumulation in bafilomycin A1 induced PC12 cells. MTT assay was used to examine the DPA effect on the viability of PC12 cells stable transfected with pCB6-APP (PC12-APP). PC12-APP cells were treated with DPA at the concentration of 6.25, 12.5, 25μg/mL for 4h, and then co-treated with 50nmol/L bafilomycin A1 for 48h except the controls. The Aβ 1-42 content in culture medium was determined by ELISA. The intracellular amount of APP, Aβ 1-42 , LC3, cathepsin D was measured by Western blotting and normalized to GAPDH loading control. The PC12 cells stable transfected with pSelect-LC3-GFP (PC12-LC3-GFP) was used in the fluorescence microscopy estimation of autophagosomes accumulation. The internal pH in lysosome was detected by LysoTracker Red staining. DPA had no significant effect on the cell viability but could significantly decrease Aβ 1-42 content in culture medium and eliminate the intracellular accumulation of APP and Aβ 1-42 in bafilomycin A1 induced PC12-APP cells. Furthermore, DPA lowered the LC3-II/LC3-I ratio and reduced the GFP-labeled LC3 puncta which were elevated by bafilomycin A1. And the increase in internal pH of lysosome and decrease in mCatD amount in Bafilomycin A1 induced PC12-APP cells were restored by DPA treatment. These results indicated that DPA could restore the lysosomal acidification and recover the autophgic flux which is impaired by bafilomycin A1. DPA could effectively clear the accumulation of Aβ 1

  5. Future technology - fuel cell and battery accumulators. Zukunftstechnologie Brennstoffzelle und Batteriespeicher

    Energy Technology Data Exchange (ETDEWEB)

    Drenckhahn, W.; Hassmann, K.; Kuehne, H.M.

    1991-09-01

    The fuel cell as an electro-chemical source of electricity fulfils the conditions of high efficiency and environmentally accetable operational method. It is thus an important energy transformation plant for the future, which has to be developed. This actually happens world-wide, and prototypes are already in operation. The authors present the mode of operation and stage of development of various fuel cells. The accumulator, too, which has an equally important duty, is still at the beginning of its development. Its present stage is also described. (orig.).

  6. A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

    Directory of Open Access Journals (Sweden)

    Rafael Romero-Calderón

    2008-11-01

    Full Text Available Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

  7. Microscopic Measurements of Axial Accumulation of Red Blood Cells in Capillary Flows Effects of Deformability

    Science.gov (United States)

    Sasaki, Takahiro; Seki, Junji; Itano, Tomoaki; Sugihara-Seki, Masako

    2017-11-01

    In the microcirculation, red blood cells (RBCs) are known to accumulate in the region near the central axis of microvessels, which is called the ``axial accumulation''. Although this behavior of RBCs is considered to originate from high deformability of RBCs, there have been few experimental studies on the mechanism. In order to elucidate the effect of RBC deformability on the axial accumulation, we measured the cross-sectional distributions of RBCs flowing through capillary tubes with a high spatial resolution by a newly devised observation system for intact and softened RBCs as well as hardened RBCs to various degrees. It was found that the intact and softened RBCs are concentrated in the small area centered on the tube axis, whereas the hardened RBCs are dispersed widely over the tube cross section dependent on the degree of hardness. These results demonstrate clearly the essential role of the deformability of RBCs in the ``axial accumulation'' of RBCs. JSPS KAKENHI Grant Number 17H03176, Kansai University ORDIST group funds.

  8. Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial

    DEFF Research Database (Denmark)

    Donskov, F; Hokland, M; Marcussen, N

    2006-01-01

    mechanism clinically in two randomised phase II trials in metastatic renal cell carcinoma (mRCC). In parallel with the clinical trial in Denmark (n=63), we obtained serial blood samples and tumour biopsies searching for a potential histamine effect in situ. At baseline and on-treatment weeks 3 and 8, we...... monitored the 'good guys' (i.e. NK and T cells) and 'bad guys' (i.e. monocytes/macrophages and neutrophils) simultaneously in blood (n=59) and tumour tissue (n=44). Patients with high number of monocytes and neutrophils in peripheral blood had very poor survival, with apparently no benefit from either IL-2...... alone or IL-2/HDC treatment. Blood monocytes (r=-0.36, P=0.01) and neutrophils (r=-0.46, P=0.001) were negatively correlated with cytotoxicity, whereas blood NK cells were positively correlated with cytotoxicity (r=0.39, P=0.002). Treatment with IL-2 alone resulted in a significantly higher number...

  9. Betulinic acid inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition.

    Science.gov (United States)

    Liu, Chun-Mei; Qi, Xue-Lin; Yang, Ya-Feng; Zhang, Xiu-de

    2016-05-01

    Glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation have been recognized as major pathogenic events in the progression of diabetic nephropathy. Betulinic acid (BA), (3β-hydroxy-lup-20(29)-en-28-oic acid), is a naturally occurring pentacyclic lupane group triterpenoid, and it has been shown to possess glucose-lowering property. However, the role of BA on MC proliferation and ECM accumulation in diabetic condition remains unclear. So, in the present study, we investigated the role of BA on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. In the current study, we demonstrated that BA suppressed HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21(Waf1/Cip1) and p27(Kip1). It also suppressed HG-induced fibronectin (FN) expression in MCs. Furthermore, BA inhibited HG-induced phosphorylation of ERK1/2 and p38MAPK in MCs. In conclusion, our present study demonstrated that BA inhibited HG-induced cell proliferation and FN expression in MCs via inhibiting ERK1/2 and p38MAPK pathways. Thus, BA may serve as a potential drug for the treatment of diabetic nephropathy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue

    Science.gov (United States)

    T-cells, particularly CD8+ T-cells, are major participants in obesity-linked adipose tissue inflammation. We examined the mechanisms of CD8+ T-cell accumulation and activation in adipose tissue and the role of CD11a, a beta2 integrin. CD8+ T-cells in adipose tissue of obese mice showed activated phe...

  11. Bixa orellana leaf extract suppresses histamine-induced endothelial hyperpermeability via the PLC-NO-cGMP signaling cascade.

    Science.gov (United States)

    Yong, Yoke Keong; Chiong, Hoe Siong; Somchit, Muhd Nazrul; Ahmad, Zuraini

    2015-10-14

    Histamine is established as a potent inflammatory mediator and it is known to increased endothelial permeability by promoting gap formation between endothelial cells. Previous studies have shown that aqueous extract of Bixa orellana leaves (AEBO) exhibits antihistamine activity in vivo, yet the mechanism of its action on endothelial barrier function remains unclear. Therefore, the current study aimed to determine the protective effect of AEBO against histamine-induced hyperpermeability in vitro. The endothelial protective effect of AEBO was assess using an in vitro vascular permeability assay kit. Human umbilical vein endothelial cells (HUVEC) were used in the current study. HUVEC were pre-treated with AEBO for 12 h before histamine induction. Vascular permeability was evaluated by the amount of FITC-dextran leakage into the lower chamber. In order to elucidate the mechanism of action of AEBO, phospholipase C (PLC) activity, intracellular calcium level, nitric oxide (NO) concentration, cyclic guanosine monophosphate (cGMP) production and protein kinase C (PKC) activity were determined following histamine challenge. Histamine-induced increased HUVEC permeability was significantly attenuated by pretreatment with AEBO in a time- and concentration-dependent manner. Upregulation of PLC activity caused by histamine in HUVEC was suppressed by pretreatment with AEBO. Pretreatment with AEBO also blocked the production of intracellular calcium induced by histamine in HUVEC. In addition, AEBO suppressed the NO-cGMP signaling cascade when HUVEC were challenged with histamine. Moreover, PKC activity was significantly abolished by pretreatment with AEBO in HUVEC under histamine condition. In conclusion, the present data suggest that AEBO could suppress histamine-induced increased endothelial permeability and the activity may be closely related with the inhibition of the PLC-NO-cGMP signaling pathway and PKC activity.

  12. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

    International Nuclear Information System (INIS)

    Monnet-Tschudi, Florianne; Hazekamp, Arno; Perret, Nicolas; Zurich, Marie-Gabrielle; Mangin, Patrice; Giroud, Christian; Honegger, Paul

    2008-01-01

    Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 μM in single treatment and of 1 μM and 2 μM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 μM of THC or JWH 015, whereas the expression of TNF-α remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation

  13. The role of histamine in the regulation of the viability, proliferation and transforming growth factor β1 secretion of rat wound fibroblasts.

    Science.gov (United States)

    Wolak, Monika; Bojanowska, Ewa; Staszewska, Teresa; Ciosek, Joanna; Juszczak, Marlena; Drobnik, Jacek

    2017-04-01

    Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFβ1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10 -8 M-10 -4 M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFβ1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10 -8 and 10 -6 M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10 -4 M) and 2-pyridylethlamine dihydrochloride increased TGFβ1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFβ1. H1 receptor expression on wound fibroblasts was confirmed. The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFβ1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  14. Symptoms of pseudoallergy and histamine metabolism disorders

    Directory of Open Access Journals (Sweden)

    Joanna Kacik

    2016-09-01

    Full Text Available Histamine intolerance is a poorly investigated type of hypersensitivity responsible for a number of often serious symptoms, erroneously interpreted as food allergy. Endogenous histamine originates from the histidine amino acid with the help of the histidine decarboxylase enzyme. Apart from the endogenous production histamine may be supplied to the body with food. Slow-maturing and fermenting products are characterised by particularly high levels of histamine. Some food products stimulate excessive release of histamine from stores in the body as well as containing significant amounts of it. These products include spices, herbs, dried fruits and a large group of food additives. Histamine intolerance is considered to be a condition in which the amount of histamine in the body exceeds its tolerance threshold, which leads to the development of adverse reactions. These reactions primarily include skin symptoms (pruritus, urticaria, skin reddening, acne lesions, angioedema, respiratory symptoms (nasal obstruction and watery discharge, sneezing, coughing, wheezing, gastrointestinal symptoms (abdominal cramps, diarrhoea, bloating, nervous system symptoms (headaches, fatigue, irritability, anxiety, panic attacks, cardiovascular symptoms (tachycardia, hypotension, chest pain, primary dysmenorrhoea and many more. It is estimated that nearly 1% of society is susceptible to histamine intolerance. The diagnosis of this disorder is based on observing at least two characteristic symptoms and their disappearance or improvement following histamine-free diet. A new, although not easily accessible diagnostic tool is assay for serum diamine oxidase activity, which correlates to a significant extent with symptoms of histamine intolerance. Normal activity of diamine oxidase is considered to be the amount of >80 HDU/mL, decreased activity – 40–80 HDU/mL and severely decreased activity – <40 HDU/mL. Currently the option of diamine oxidase supplementation is

  15. Effects of auxins on growth and scopoletin accumulation in cell suspension cultures of Angelica archangelica L.

    Science.gov (United States)

    Siatka, T; Kasparová, M

    2008-01-01

    Scopoletin is a coumarin possessing many interesting biological effects, e.g., spasmolytic, anti-inflammatory, antimutagenic, antioxidant, antifungal, apoptosis-inducing, antiproliferative, acetylcholinesterase-inhibitory, and hypouricemic activities. Plant tissue cultures represent a promising alternative source of valuable plant-derived substances. A number of physical and chemical factors influence the cell growth and secondary metabolite biosynthesis in plant tissue cultures. The mechanism of their action is not completely understood. Besides other factors, plant growth regulators and light conditions play an important role. Effects of four auxins (2,4-dichlorophenoxyacetic acid, 2,4-D, alpha-naphthaleneacetic acid, NAA, beta-indoleacetic acid, IAA or beta-indolebutyric acid, IBA) at four concentrations (0.2, 2, 10 or 20 mg/l) on the culture growth and accumulation of scopoletin in the medium were tested in Angelica archangelica cell suspension cultures cultured under continuous light or in the dark. The highest culture growth was achieved with 2 mg/l 2,4-D, and 10 mg/l IAA. The best scopoletin levels were obtained with 0.2 mg/l 2,4-D, 2 mg/l 2,4-D, 10 mg/l NAA, and 20 mg/l IAA. The effects of light conditions were less marked than those of auxins and their concentrations in influencing both the cell growth and scopoletin accumulation in Angelica archangelica cell suspension cultures. The changes brought about by auxins were modified by light conditions.

  16. Different perception levels of histamine-induced itch sensation in young adult mice.

    Science.gov (United States)

    Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

    2018-05-01

    Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Histamine stimulates secretion of extracellular vesicles with nucleotidase activity in rat submandibular gland.

    Science.gov (United States)

    González, Débora Alejandra; Barbieri van Haaster, Martín Matías; Quinteros Villarruel, Emmanuel; Brandt, Macarena; Benítez, María Belén; Stranieri, Graciela Mabel; Orman, Betina

    2018-01-01

    Extracellular vesicles released by different cells have been isolated from diverse fluids including saliva. We previously reported that rat submandibular glands secrete nanovesicles that catalyze hydrolysis of ATP, ADP and AMP, which are actors of the purinergic signaling system along with adenosine. Extracellular nucleotides like ATP and adenosine are involved in the regulation of inflammatory processes and apoptosis. Histamine, a widely distributed biogenic amine, is involved in inflammatory response. To test if activation of histamine receptors in rat submandibular gland promotes changes in the release of vesicles with nucleotidase activity that could modulate purinergic signaling. Rat submandibular glands were incubated in the absence or presence of histamine and JNJ7777120, an antagonist for H 4 receptors. Extracellular vesicles were isolated from incubation media by differential centrifugation. Vesicular nucleotidase activity was measured following Pi release by 3mM MgATP, MgADP or MgAMP. Histamine increased the release of vesicles with nucleotidase activity in a concentration dependent manner. JNJ7777120 significantly reduced this effect. Vesicular nucleotidases obtained in the absence or presence of histamine promoted Pi production from ATP, ADP and AMP. The results show a relationship between histamine and the regulation of purinergic signaling, which could be important in the modulation of inflammatory processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The relationship between energy metabolism and the action of inhibitors of histamine release

    DEFF Research Database (Denmark)

    Garland, L G; Johansen, Torben

    1977-01-01

    1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol/l) and dicu......1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol...... of histamine release from mast cells incubated in glucose-free solution than in complete Tyrode solution (dose-ratio = 20). Like antimycin A (L MICRONMOL/L), PAPAVERINE (3 MICRONMOL/L) CAUSED A DEPLETION OF MAST CELL ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose....... 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis. 5 Inhibition of histamine release by dibutyryl...

  19. Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation.

    Science.gov (United States)

    Veglia, Eleonora; Grange, Cristina; Pini, Alessandro; Moggio, Aldo; Lanzi, Cecilia; Camussi, Giovanni; Chazot, Paul L; Rosa, Arianna Carolina

    2015-04-01

    The aim of this study is to evaluate the expression of the histamine receptors, particularly focusing on the H4R in human renal tubules. The ex vivo evaluation was carried on specimens from human renal cortex. Primary and immortalized tubular epithelial cells (TECs) and the HK-2 cell line were used as in vitro models. Cells were pretreated for 10 min with chlorpheniramine maleate 10 μM (H1R antagonist), ranitidine 10 µM (H2R antagonist), GSK189254 1 µM (H3R antagonist) or JNJ7777120 10 µM (H4R antagonist), and then exposed to histamine (3 pM-10 nM) for 30 min. The ex vivo evaluation on specimens from human renal cortex was performed by immunohistochemistry. The expression of histamine receptors on primary and immortalized TECs and the HK-2 cell line was evaluated at both gene (RT-PCR) and protein (immunocytofluorescence) levels. The pharmacological analysis was performed by TR-FRET measurements of second messenger (IP3 and cAMP) production induced by histamine with or without the selective antagonists. Our data revealed the presence of all histamine receptors in human tubules; however, only TECs expressed all the receptors. Indeed, histamine elicited a sigmoid dose-response curve for IP3 production, shifted to the right by chlorpheniramine maleate, and elicited a double bell-shaped curve for cAMP production, partially suppressed by the selective H2R, H3R and H4R antagonists when each added alone, and completely ablated when combined together. Herein, we report the identification of all four histamine receptors in human renal tubules.

  20. Wheat cells accumulate a syringyl-rich lignin during the hypersensitive resistance response.

    Science.gov (United States)

    Menden, Barbara; Kohlhoff, Markus; Moerschbacher, Bruno M

    2007-02-01

    The stem rust fungus Puccinia graminis f.sp. tritici is an obligately biotrophic pathogen attacking wheat (Triticum aestivum). In compatible host/pathogen-interactions, the fungus participates in the host's metabolism by establishing functional haustoria in the susceptible plant cells. In highly resistant wheat cultivars, fungal attack is stopped by a hypersensitive response of penetrated host cells. This mechanism of programmed cell death of single plant cells is accompanied by the intracellular accumulation of material with UV-fluorescence typical of phenolic compounds. A similar reaction can be induced in healthy wheat leaves by the application of a rust-derived elicitor. We analysed the biochemical composition of this defense-induced phenolic material. Contents of total soluble and cell wall esterified and etherified phenolic acids were determined in rust-inoculated and elicitor-treated leaves of the fully susceptible wheat cultivar Prelude and its highly resistant, near-isogenic line Prelude-Sr5. While no resistance-related changes occured in any of these fractions, the lignin content as determined by the thioglycolic acid and the acetyl bromide methods increased after elicitor treatment. Nitrobenzene oxidation revealed that the entire increase can be explained by an increase in syringyl units only. These biochemical data were confirmed by fluorescence emission spectra analyses which indicated a defense-induced enrichment of syringyl lignin for cell wall samples both from elicitor-treated wheat leaves and single host cells undergoing a hypersensitive response upon fungal penetration.

  1. Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity.

    Science.gov (United States)

    Westerterp, Marit; Gautier, Emmanuel L; Ganda, Anjali; Molusky, Matthew M; Wang, Wei; Fotakis, Panagiotis; Wang, Nan; Randolph, Gwendalyn J; D'Agati, Vivette D; Yvan-Charvet, Laurent; Tall, Alan R

    2017-06-06

    Autoimmune diseases such as systemic lupus erythematosus (SLE) are associated with increased cardiovascular disease and reduced plasma high-density lipoprotein (HDL) levels. HDL mediates cholesterol efflux from immune cells via the ATP binding cassette transporters A1 and G1 (ABCA1/G1). The significance of impaired cholesterol efflux pathways in autoimmunity is unknown. We observed that Abca1/g1-deficient mice develop enlarged lymph nodes (LNs) and glomerulonephritis suggestive of SLE. This lupus-like phenotype was recapitulated in mice with knockouts of Abca1/g1 in dendritic cells (DCs), but not in macrophages or T cells. DC-Abca1/g1 deficiency increased LN and splenic CD11b + DCs, which displayed cholesterol accumulation and inflammasome activation, increased cell surface levels of the granulocyte macrophage-colony stimulating factor receptor, and enhanced inflammatory cytokine secretion. Consequently, DC-Abca1/g1 deficiency enhanced T cell activation and T h 1 and T h 17 cell polarization. Nlrp3 inflammasome deficiency diminished the enlarged LNs and enhanced T h 1 cell polarization. These findings identify an essential role of DC cholesterol efflux pathways in maintaining immune tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

    Science.gov (United States)

    Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

    2018-01-01

    oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

  3. Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line

    Energy Technology Data Exchange (ETDEWEB)

    Miyamae, Yusaku, E-mail: ymiyamae@lif.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nishito, Yukina; Nakai, Naomi [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nagumo, Yoko; Usui, Takeo [Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki 305-8572 (Japan); Masuda, Seiji; Kambe, Taiho [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan); Nagao, Masaya, E-mail: mnagao@kais.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Oiwakecho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan)

    2016-08-12

    Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis. We found that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra, induced lipid accumulation, a phenotype associated with quiescent HSCs, through blockade of autophagy in the rat-derived HSC line HSC-T6. Tetrandrine inhibited autophagic flux without affecting lysosomal function. A phenotypic comparison using siRNA knockdown suggested that tetrandrine may target regulators, involved in fusion between autophagosomes and lysosomes (e.g., syntaxin 17). Moreover, perilipin 1, an LD-coated protein, co-localized specifically with LC3, a marker protein for autophagosomes, in tetrandrine-treated HSC-T6 cells. This suggests a potential role for perilipin 1 in autophagy-mediated LD degradation in HSCs. Our results identified tetrandrine as a potential tool for prevention and treatment of HSC activation. - Highlights: • Autophagy is closely related to lipid degradation in hepatic stellate cells. • Tetrandrine (Tet) causes lipid accumulation via blockade of autophagy in HSC-T6 cells. • Tet blocked autophagy without affecting lysosomal function unlike bafilomycin A{sub 1}. • Perilipin 1 was specifically co-localized with LC3 in Tet-treated cells. • Perilipin 1 may play potential roles in autophagy-mediated lipid degradation.

  4. Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer

    International Nuclear Information System (INIS)

    Forghani, Parvin; Khorramizadeh, Mohammad R; Waller, Edmund K

    2014-01-01

    Myeloid-derived suppressor cells (MDSC)s increase in blood and accumulate in the tumor microenvironment of tumor-bearing animals, contributing to immune suppression in cancer. Silibinin, a natural flavonoid from the seeds of milk thistle, has been developed as an anti-inflammatory agent and supportive care agent to reduce the toxicity of cancer chemotherapy. The goals of this study were to evaluate the effect of silibinin on MDSCs in tumor-bearing mice and antitumor activity of silibinin in a mouse model of breast cancer. 4T1 luciferase-transfected mammary carcinoma cells were injected into in the mammary fat pad female BALB/c mice, and female CB17-Prkdc Scid/J mice. Silibinin treatment started on day 4 or day 14 after tumor inoculation continued every other day. Tumor growth was monitored by bioluminescent imaging (BLI) measuring total photon flux. Flow cytometry measured total leukocytes, CD11b + Gr-1 + MDSC, and T cells in the blood and tumors of tumor-bearing mice. The effects of silibinin on 4T1 cell viability in vitro were measured by BLI. Treatment with silibinin increased overall survival in mice harboring tumors derived from the 4T1-luciferase breast cancer cell line, and reduced tumor volumes and numbers of CD11b + Gr-1 + MDSCs in the blood and tumor, and increased the content of T cells in the tumor microenvironment. Silibinin failed to inhibit tumor growth in immunocompromised severe combined immunodeficiency mice, supporting the hypothesis that anticancer effect of silibinin is immune-mediated. The antitumor activity of silibinin requires an intact host immune system and is associated with decreased accumulation of blood and tumor-associated MDSCs

  5. The actions of methacholine, phenylephrine, salbutamol and histamine on mucus secretion from the ferret in-vitro trachea.

    Science.gov (United States)

    Webber, S E; Widdicombe, J G

    1987-10-01

    Methacholine, phenylephrine and histamine produced highly significant and salbutamol significant increases in the rate of mucus secretion from the ferret trachea. Methacholine, phenylephrine and histamine all produced highly significant increases in the rate of output of lysozyme, but the concentration of lysozyme in the mucus was significantly increased only by phenylephrine. Salbutamol produced no significant change in the output of lysozyme, and the concentration of lysozyme in the mucus was significantly decreased. It is concluded that methacholine, phenylephrine and histamine are potent stimulators of serous cell secretion whereas salbutamol has only a weak secretory action on these cells. Methacholine, histamine and salbutamol probably stimulate secretion from mucous cells as well as from serous cells. The increase in the concentration of lysozyme produced by phenylephrine may be due to stimulation of a fluid reabsorption mechanism.

  6. Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor.

    Science.gov (United States)

    Andersson, Richard; Galter, Dagmar; Papadia, Daniela; Fisahn, André

    2017-05-15

    Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are closely associated with gamma oscillations, a rhythmical electrical activity pattern in the 30-80 Hz range, which depends on the synchronized activity of excitatory pyramidal cells and inhibitory fast-spiking interneurons. We set out to explore whether histamine has a role in promoting gamma oscillations in the hippocampus. Using in-situ hybridization we demonstrate that histamine receptor subtypes 1, 2 and 3 are expressed in stratum pyramidale of area CA3 in rats. We show that both pyramidal cells and fast-spiking interneurons depolarize and increase action potential firing in response to histamine in vitro. The activation of histamine receptors generates dose-dependent, transient gamma oscillations in area CA3 of the hippocampus - the locus of the gamma rhythm generator. We also demonstrate that this histamine effect is independent of muscarinic receptors. Using specific antagonists we provide evidence that histamine gamma rhythmogenesis specifically depends on the H1 receptor. Histamine also depolarized both pyramidal cells and fast-spiking interneurons and increased membrane resistance in pyramidal cells. The increased membrane resistance is potentially mediated by the inhibition of potassium channels because application of the KCNQ channel opener ICA110381 abolished the oscillations. Taken together our data demonstrate a novel and physiological mechanism for generating gamma oscillations in hippocampus and suggest a role for KCNQ channels in this cognition-relevant brain activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes.

    Science.gov (United States)

    Boonen, Marielle; van Meel, Eline; Oorschot, Viola; Klumperman, Judith; Kornfeld, Stuart

    2011-04-15

    We previously reported that mice deficient in UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase (mucolipidosis type II or Gnptab -/- mice), the enzyme that initiates the addition of the mannose 6-phosphate lysosomal sorting signal on acid hydrolases, exhibited extensive vacuolization of their exocrine gland cells, while the liver, brain, and muscle appeared grossly unaffected. Similar pathological findings were observed in several exocrine glands of patients with mucolipidosis II. To understand the basis for this cell type-specific abnormality, we analyzed these tissues in Gnptab -/- mice using a combined immunoelectron microscopy and biochemical approach. We demonstrate that the vacuoles in the exocrine glands are enlarged autolysosomes containing undigested cytoplasmic material that accumulate secondary to deficient lysosomal function. Surprisingly, the acid hydrolase levels in these tissues ranged from normal to modestly decreased, in contrast to skin fibroblasts, which accumulate enlarged lysosomes and/or autolysosomes also but exhibit very low levels of acid hydrolases. We propose that the lysosomal defect in the exocrine cells is caused by the combination of increased secretion of the acid hydrolases via the constitutive pathway along with their entrapment in secretory granules. Taken together, our results provide new insights into the mechanisms of the tissue-specific abnormalities seen in mucolipidosis type II.

  8. Photocharge accumulation and recombination in perovskite solar cells regarding device performance and stability

    Science.gov (United States)

    Li, Yusheng; Li, Yiming; Shi, Jiangjian; Li, Hongshi; Zhang, Huiyin; Wu, Jionghua; Li, Dongmei; Luo, Yanhong; Wu, Huijue; Meng, Qingbo

    2018-01-01

    Photocharge accumulation and recombination in perovskite solar cells have been systematically investigated in this paper by electrochemical spectroscopy and transient photocurrent/photovoltage methods. It is found that the non-equilibrium photocharges stored in the selective charge transport layers follow a backward recombination mechanism. That is, the photocharges are first captured by the interface defects corresponding to the fast photovoltage decay, while the bulk charge recombination instead of the diffusion process dominates the slow photovoltage decay process. Further investigation reveals that the device degradation preferentially takes place at the interface under working conditions, which thus can confirm the importance of interface engineering to enhance the device stability.

  9. Study of Plant Cell Wall Polymers Affected by Metal Accumulation Using Stimulated Raman Scattering Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Shi-You [Harvard Univ., Cambridge, MA (United States)

    2015-03-02

    This project aims to employ newly-developed chemical imaging techniques to measure, in real-time, the concentration, dynamics and spatial distribution of plant cell wall polymers during biomass growth with inoculation of transgenic symbiotic fungi, and to explore a new pathway of delivering detoxified metal to plant apoplast using transgenic symbiotic fungi, which will enhance metal accumulation from soil, and potentially these metals may in turn be used as catalysts to improve the efficiency of biomass conversion to biofuels. The proposed new pathway of biomass production will: 1) benefit metal and radionuclide contaminant mobility in subsurface environments, and 2) potentially improve biomass production and process for bioenergy

  10. Vacuolar accumulation of heavy metals in Datura cultured cells is metal concentration dependent

    International Nuclear Information System (INIS)

    Krotz, R.M.; Wagner, G.J.

    1987-01-01

    Vacuolar-extravacuolar compartmentation studies were performed to determine if the vacuole serves as an accumulation site for Cd, Zn, and Ni, after growth of Datura cultured cells in trace and high levels of these metals. After 3 to 4 days growth with 0.12 μM Cd or 0.02 μM Ni (radiolabeled) no evidence was obtained for vacuolar accumulation of these metals. In contrast, growth with 30 or 45 μM Cd, 11 μM Ni (with or without trace radiolabel), or 300 and 500 μM Zn resulted in isolated vacuoles which were enriched in metal. Compartmentation after exposure to low levels of Zn and also Cu is being investigated as is the subcellular site(s) of Cd-binding peptide formed during growth in high Cd. The hypothesis that Zn is accumulated as vacuolar organic acid salts is being tested directly because no evidence was found for formation of substantial ligand of Cd-peptide in response to Zn exposure

  11. What Will the New Generation Generate? Gendering Accumulation in Fatou Diome’s Celles qui attendent

    Directory of Open Access Journals (Sweden)

    Christopher Hogarth

    2014-01-01

    Full Text Available In this paper I focus on the penultimate installment of the oeuvre of the much-celebrated Franco-Senegalese writer Fatou Diome, whose largely autobiographical work has garnered a wide following and a lucrative contract with the Flammarion publishing house. I propose that Diome’s 2010 novel Celles qui attendent strongly contributes to a discourse surrounding the roles of males and females in an African economy increasingly dominated by migration. Diome started as a writer who portrayed the empowered role of the female migrant, who is able to accumulate financial capital in Europe and send it back to Africa in order for males to slowly hoard goods and start businesses. Her more recent work, however, has been marked by a shift to reflect a portrait of Senegalese society and migration that is backed by sociological studies: men take on the role of migrants, tempted by “marchands d’illusions” 'merchants of illusions,' but are also determined to get away from social pressures in order to accumulate their own set of experiences in the world, at a distance from the expectations of a traditional African society. Women, on the other hand, are left in extreme proximity to the problems of everyday life on a cash-starved continent, as they have to go about the business of surviving and raising children, engaging in many forms of hoarding that have to do with accumulating finance, memories and myths.

  12. Caffeoylquinic Acids Generated In Vitro in a High-Anthocyanin-Accumulating Sweet potato Cell Line

    Directory of Open Access Journals (Sweden)

    Izabela Konczak

    2004-01-01

    Full Text Available Accumulation of phenolic compounds has been monitored in a suspension culture of anthocyanin-accumulating sweet potato cell line grown under the conditions of modified Murashige and Skoog high-anthocyanin production medium (APM over a period of 24 days. Tissue samples extracted with 15% acetic acid were analysed using HPLC at a detection wavelength of 326 nm. Among others, the following derivatives of caffeoylquinic acids were detected: 4,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 3,4,5-tricaffeoylquinic acid. Their total amount reached a maximum of 110 mg/gFW between the 4th and the 15th day of culture growth on APM. The major compound of the phenolic mixture was 3,5-dicaffeoylquinic acid with maximum accumulation level of 80 mg/100 gFW. The potential effects of targeted phenolic compounds on the nutraceutical qualities of in vitro produced anthocyanin-rich extracts are discussed.

  13. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

    Directory of Open Access Journals (Sweden)

    Laurie-Anne Payet

    Full Text Available The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF, leads to the retention of the protein in the endoplasmic reticulum (ER. The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(- cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.

  14. Light spectrum regulates cell accumulation during daytime in the raphidophyte Chattonella antiqua causing noxious red tides.

    Science.gov (United States)

    Shikata, Tomoyuki; Matsunaga, Shigeru; Kuwahara, Yusuke; Iwahori, Sho; Nishiyama, Yoshitaka

    2016-07-01

    Most marine raphidophyte species cause noxious red tides in temperate coastal areas around the world. It is known that swimming abilities enable raphidophytes to accumulation of cells and to actively acquire light at surface layers and nutrients over a wide depth range. However, it remains unclear how the swimming behavior is affected by environmental conditions, especially light condition. In the present study, we observed the accumulation of the harmful red-tide raphidophyte Chattonella antiqua under various light conditions during the daytime in the laboratory. When exposed to ultraviolet-A/blue light (320-480nm) or red light (640-680nm) from above, cells moved downward. In the case of blue light (455nm), cells started to swim downward after 5-15min of irradiation at a photon flux density≥10μmolm(-2)s(-1). When exposed to monochromatic lights (400-680nm) from the side, cells moved away from the blue light source and then descended, but just moved downward under red light. However, mixing of green/orange light (520-630nm) diminished the effects of blue light. When exposed to a mixture of 30μmolm(-2)s(-1) of blue light (440nm) and ≥6μmolm(-2)s(-1) of yellow light (560nm) from above, cells did not move downward. These results indicate that blue light induces negative phototaxis and ultraviolet-A/blue and red lights induce descending, and green/orange light cancels out their effects in C. antiqua. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Microstructures and functional groups of Nannochloropsis sp. cells with arsenic adsorption and lipid accumulation.

    Science.gov (United States)

    Sun, Jing; Cheng, Jun; Yang, Zongbo; Li, Ke; Zhou, Junhu; Cen, Kefa

    2015-10-01

    The pore structures and surface morphological characteristics of Nannochloropsis sp. cells with arsenic adsorption were initially investigated by N2-adsorption analysis and scanning electronic microscopy. Functional groups of cells were analysed by Fourier-transform infrared spectrometry and X-ray photoelectron spectroscopy. Total surface area of microalgal cells increased from 0.54 m(2)/g to 1.80 m(2)/g upon arsenic adsorption. The external cell surface area increased. More wrinkles and measles-like granules formed on the surfaces as a result of arsenic toxicity. Arsenic ions blocked cell pores and decreased the average pore diameter and total pore volume. Ether cross-linked structures in the algaenan layer of cell walls were disrupted as the percentage of C-O functional groups decreased. These functional groups underwent complexation reactions with arsenic ions. Accumulation of polyunsaturated fatty acids decreased because of oxidative stresses induced by arsenic. The increase in generation of short-chain saturated fatty acids was favourable for the production of quality biodiesel. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Lack of cortical endoplasmic reticulum protein Ist2 alters sodium accumulation in Saccharomyces cerevisiae cells.

    Science.gov (United States)

    Papouskova, Klara; Andrsova, Marketa; Sychrova, Hana

    2017-03-01

    The maintenance of intracellular alkali-metal-cation homeostasis is a fundamental property of all living organisms, including the yeast Saccharomyces cerevisiae. Several transport systems are indispensable to ensure proper alkali-metal-cation levels in the yeast cytoplasm and organelles. Ist2 is an endoplasmic reticulum (ER)-resident protein involved, together with other tethering proteins, in the formation of contacts between the plasma and ER membranes. As IST2 gene deletion was shown to influence yeast growth in the presence of sodium, we focused on the roles of Ist2 in the cell response to the presence of various concentrations of alkali metal cations, and its interactions with characterised plasma membrane alkali-metal-cation transporters. Most importantly, we show that, in BY4741 background, the lack of Ist2 results in the accumulation of higher amounts of sodium when the cells are exposed to the presence of this cation, demonstrating the importance of Ist2 for the maintenance of low intracellular levels of toxic sodium. As the function and localisation of alkali-metal-cation exporters is not affected in ist2Δ cells, IST2 deletion results in an increased non-specific uptake of sodium to cells. Moreover, the deletion of IST2 influences relative cell membrane potential, pHin and the growth of cells in the presence of a limiting K+ concentration. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    Science.gov (United States)

    Vicari, Luisa; Musumeci, Teresa; Giannone, Ignazio; Adamo, Luana; Conticello, Concetta; De Maria, Ruggero; Pignatello, Rosario; Puglisi, Giovanni; Gulisano, Massimo

    2008-01-01

    Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested. Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies. PMID:18657273

  18. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity.

    Science.gov (United States)

    Vicari, Luisa; Musumeci, Teresa; Giannone, Ignazio; Adamo, Luana; Conticello, Concetta; De Maria, Ruggero; Pignatello, Rosario; Puglisi, Giovanni; Gulisano, Massimo

    2008-07-25

    PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested. These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  19. Accumulation of ubiquitinated proteins in mouse neuronal cells induced by oxidative stress.

    Science.gov (United States)

    Figueiredo-Pereira, M E; Yakushin, S; Cohen, G

    1997-03-01

    Ubiquitin protein conjugates are commonly detected in neuronal brain inclusions of patients with neurodegenerative disorders. The failure to eliminate the ubiquitin-protein deposits in the degenerating neurons may result from changes in the activity of the ubiquitin/ATP-dependent proteolytic pathway. This proteolytic pathway plays a major role in the degradation of short lived, abnormal and denatured proteins. Cadmium is a potent cell poison and is known to affect the ubiquitin pathway and to cause oxidative stress. Increases in protein mixed-disulfides (Pr-SSG) and decreases in glutathione (GSH) are often used as markers of oxidative stress. To investigate the relationship between the ubiquitin pathway and cellular glutathione (GSH), we treated HT4 cells (a mouse neuronal cell line) and rat mesencephalic primary cultures with different concentrations of the heavy metal. We observed marked increases in Pr-SSG as well as decreases in GSH, after exposure of HT4 cells or primary mesencephalic cultures to Cd2+. Furthermore, our results show that Cd2+ induced the accumulation of ubiquitinated proteins. Detection was by Western blotting of total cell extracts probed with antibodies that recognize ubiquitin-protein conjugates. These results suggest that the ubiquitin-pathway is closely involved in the cell response to cadmium-mediated oxidative stress.

  20. Uncoupled defense gene expression and antimicrobial alkaloid accumulation in elicited opium poppy cell cultures.

    Science.gov (United States)

    Facchini, P J; Johnson, A G; Poupart, J; de Luca, V

    1996-01-01

    Treatment of opium poppy (Papaver somniferum L.) cell cultures with autoclaved mycelial homogenates of Botrytis sp. resulted in the accumulation of sanguinarine. Elicitor treatment also caused a rapid and transient induction in the activity of tyrosine/dopa decarboxylase (TYDC, EC 4.1.1.25), which catalyzes the conversion of L-tyrosine and L-dopa to tyramine and dopamine, respectively, the first steps in sanguinarine biosynthesis. TYDC genes were differentially expressed in response to elicitor treatment. TYDC1-like mRNA levels were induced rapidly but declined to near baseline levels within 5 h. In contrast, TYDC2-like transcript levels increased more slowly but were sustained for an extended period. Induction of TYDC mRNAs preceded that of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) mRNAs. An elicitor preparation from Pythium aphanidermatum was less effective in the induction of TYDC mRNA levels and alkaloid accumulation; however, both elicitors equally induced accumulation of PAL transcripts. In contrast, treatment with methyl jasmonate resulted in an induction of TYDC but not PAL mRNAs. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and the protein kinase inhibitor staurosporine partially blocked the fungal elicitor-induced accumulation of sanguinarine. However, only staurosporine and okadaic acid, an inhibitor of protein phosphatases 1 and 2A, blocked the induction of TYDC1-like transcript levels, but they did not block the induction of TYDC2-like or PAL transcript levels. These data suggest that activation mechanisms for PAL, TYDC, and some later sanguinarine biosynthetic enzymes are uncoupled. PMID:8754678

  1. New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis.

    Directory of Open Access Journals (Sweden)

    Maria Francisca eEiriz

    2014-06-01

    Full Text Available The subventricular zone (SVZ contains neural stem cells (NSCs that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB. This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine.

  2. Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.

    Science.gov (United States)

    Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V

    2010-03-24

    The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.

  3. Pro- and anti-inflammatory effects of histamine on tissue factor and TNFα expression in monocytes of human blood.

    Science.gov (United States)

    Østerud, Bjarne; Olsen, Jan Ole

    2014-03-01

    Histamine is classified as an inflammatory mediator and has been reported to have anti- as well as pro-inflammatory properties. The aim of this study was to explore the role of histamine on the production of LPS-induced tissue factor (TF) activity and TNFα in monocytes of whole blood in the absence and presence of TNFα or PMA. Human blood anticoagulated with Fragmin was subjected to stimulation by LPS in the presence and absence of TNFα or PMA and various concentrations of histamine. Tissue factor (TF) activity was measured in lyzed cells after isolation of mononuclear cells whereas TNFα was quantified in plasma after centrifugation of cells. Histamine gave a dose dependent inhibitory effect on LPS-induced TF activity in monocytes of whole blood, with a 50% reduction at 0.033 μM. A similar effect was seen when the blood cells were stimulated with the combination of LPS and TNFα although TNFα enhanced LPS-induced TF activity almost two fold. In contrast, when blood was incubated with LPS and PMA in whole blood, histamine gave a significant rise in TF activity at 0.01 μM and 0.33 μM histamine. The effect of histamine was less at 0.1 μM or higher concentrations giving a biphasic profile. Contrary to the effect of histamine on LPS plus PMA induced TF activity, histamine caused a significant reduction in TNFα albeit less than in the absence of PMA. Intake of aspirin caused a significant rise in LPS-induced TF activity that was almost abolished by histamine at 0.033 μM. Our study shows that histamine has an anti-inflammatory effect on LPS and LPS/TNFα stimulated monocytes of whole blood. In contrast when blood cells are activated by a combination of LPS and PMA whereby PKC is activated, histamine has a procoagulant/pro-inflammatory effect through enhancement of TF activity expression. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Histamine Receptor 2 is Required to Suppress Innate Immune Responses to Bacterial Ligands in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Smolinska, Sylwia; Groeger, David; Perez, Noelia Rodriguez; Schiavi, Elisa; Ferstl, Ruth; Frei, Remo; Konieczna, Patrycja; Akdis, Cezmi A; Jutel, Marek; OʼMahony, Liam

    2016-07-01

    Histamine is a key immunoregulatory mediator in immediate-type hypersensitivity reactions and chronic inflammatory responses, in particular histamine suppresses proinflammatory responses to bacterial ligands, through histamine receptor 2 (H2R). The aim of this study was to investigate the effects of histamine and H2R on bacteria-induced inflammatory responses in patients with IBD. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with Crohn's disease, patients with ulcerative colitis, and healthy controls. PBMC histamine receptor expression was evaluated by flow cytometry. Cytokine secretion following Toll-like receptor (TLR)-2, TLR-4, TLR-5, or TLR-9 stimulation in the presence or absence of histamine or famotidine (H2R antagonist) was quantified. Biopsy histamine receptor gene expression was evaluated using reverse transcription-polymerase chain reaction. The in vivo role of H2R was evaluated in the T-cell transfer murine colitis model. The percentage of circulating H2R monocytes was significantly reduced in patients with IBD. Histamine effectively suppressed TLR-induced cytokine secretion from healthy volunteer PBMCs but not for PBMCs from patients with IBD. Famotidine reversed this suppressive effect. H1R, H2R, and H4R gene expression was increased in inflamed gastrointestinal mucosa compared with noninflamed mucosa from the same patient and expression levels correlated with proinflammatory cytokine gene expression. Mice receiving lymphocytes from H2R donors, or treated with famotidine, displayed more severe weight loss, higher disease scores and increased numbers of mucosal IFN-γ and IL-17 T cells. Patients with IBD display dysregulated expression of histamine receptors, with diminished anti-inflammatory effects associated with H2R signaling. Deliberate manipulation of H2R signaling may suppress excessive TLR responses to bacteria within the gut.

  5. Pharmacological investigation into the effects of histamine and histamine analogues on guinea-pig and rat colon in vitro.

    OpenAIRE

    Aguilar, M. J.; Morales-Olivas, F. J.; Rubio, E.

    1986-01-01

    The effects of histamine and specific histamine agonists has been examined on isolated longitudinal colon strips of guinea-pig and rat. Histamine and 2-pyridyl-ethylamine but not 4 methylhistamine produced a concentration-related contractile response in the guinea-pig colon. The H1-antagonist clemizole antagonized competitively the effect of histamine but the H2-antagonist ranitidine did not modify the dose-response curve to histamine in the guinea-pig colon. Atropine, hexamethonium, prazosin...

  6. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction

    International Nuclear Information System (INIS)

    Johnson-Lyles, Denise N.; Peifley, Kimberly; Lockett, Stephen; Neun, Barry W.; Hansen, Matthew; Clogston, Jeffrey; Stern, Stephan T.; McNeil, Scott E.

    2010-01-01

    Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C 60 OH x ), are currently under development for diagnostic and therapeutic biomedical applications in the field of nanotechnology. These molecules have been shown to undergo urinary clearance, yet there is limited data available on their renal biocompatibility. Here we examine the biological responses of renal proximal tubule cells (LLC-PK1) exposed to fullerenol. Fullerenol was found to be cytotoxic in the millimolar range, with viability assessed by the sulforhodamine B and trypan blue assays. Fullerenol-induced cell death was associated with cytoskeleton disruption and autophagic vacuole accumulation. Interaction with the autophagy pathway was evaluated in vitro by Lysotracker Red dye uptake, LC3-II marker expression and TEM. Fullerenol treatment also resulted in coincident loss of cellular mitochondrial membrane potential and ATP depletion, as measured by the Mitotracker Red dye and the luciferin-luciferase assays, respectively. Fullerenol-induced ATP depletion and loss of mitochondrial potential were partially ameliorated by co-treatment with the autophagy inhibitor, 3-methyladenine. In vitro fullerenol treatment did not result in appreciable oxidative stress, as measured by lipid peroxide and glutathione content. Based on these data, it is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity. As nanoparticle-induced cytoskeleton disruption, autophagic vacuole accumulation and mitochondrial dysfunction are commonly reported in the literature, the proposed mechanism may be relevant for a variety of nanomaterials.

  7. Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy

    Directory of Open Access Journals (Sweden)

    Shashank Masaldan

    2018-06-01

    Full Text Available Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation. The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc. and metabolic disorders (e.g. diabetes. We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF, human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1, diminished levels of copper-transporting ATPase 1 (Atp7a (copper export and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH, superoxide dismutase 1 (SOD1 and glutaredoxin 1 (Grx1. The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mobr MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease. Keywords: Senescence, Copper, Ageing, Homeostasis, Autophagy

  8. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    Directory of Open Access Journals (Sweden)

    De Maria Ruggero

    2008-07-01

    Full Text Available Abstract Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w had a mean size Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  9. The effect of histamine on kidney by fasting in rats.

    Science.gov (United States)

    Gurgen, S G; Erdogan, D; Take-Kaplanoglu, G

    2013-01-01

    The aim of this study was to investigate ultrastructural and apoptotic changes occurring in the kidneys in fasting individuals and to examine the effects of histamine treatment at the electron-microscopic and immunohistochemical levels. Eighteen adult Wistar male rats were randomly divided into three groups (n=6 for each). Control group (1), fasting group (12 h) (2), and fasting+histamine injection (0.5 mg/kg) (3) group. Expression of caspase-3 and caspase-9 was determined in the tissue sections using immunohistochemical techniques. Quantitative data were obtained using H-SCORE, and statistical evaluations were then performed. The ultrastructure of the kidney tissues was examined using transmission electron microscopy. Weak caspase-3 and caspase-9 expression was observed in the renal tubules and glomeruli in the control group, while immunoreactivity was more intense in the fasting group (phistamine group, caspase-3 and caspase-9 immunostaining was significantly positive in both renal tubules and glomeruli (phistamine group, in addition to significant dilatation of all glomerular capillaries, there were degenerative changes in all tubular and canalicular epithelial cells in the proximal tubules. Fasting, an important metabolic stress factor, accompanied by histamine treatment may cause significant disruptions in the kidneys, particularly in the glomerular capillaries and proximal and distal tubules (Tab. 1, Fig. 2, Ref. 34).

  10. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

    Directory of Open Access Journals (Sweden)

    D. Remirez

    2002-01-01

    Full Text Available It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300 mg/kg post-orally (p.o. was administered 1 h before the challenge with 1 μg of ovalbumin (OA in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o. also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phyco-cyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

  11. Stimulation of the histamine 4 receptor upregulates thymic stromal lymphopoietin (TSLP) in human and murine keratinocytes.

    Science.gov (United States)

    Schaper, Katrin; Rossbach, Kristine; Köther, Brigitta; Stark, Holger; Kietzmann, Manfred; Werfel, Thomas; Gutzmer, Ralf

    2016-11-01

    The cytokine thymic stromal lymphopoietin (TSLP) is involved in the development and the progression of allergic diseases. It is mainly released by epithelial cells at barriers such as skin and gut in response to danger signals. Overexpression of TSLP in keratinocytes (KC) can provoke the development of a type 2 inflammatory response. Additionally, TSLP directly acts on sensory neurons and thereby triggers itch. Since histamine is also increased in lesions of inflammatory skin diseases, the aim of this study was to investigate possible effects of histamine as well as different histamine receptor subtype agonists and antagonists on TSLP production in KC. We therefore stimulated human KC with histamine in the presence or absence of the known TSLP-inductor poly I:C and measured TSLP production at protein as well as mRNA level. Histamine alone did not induce TSLP production in human KC, but pre-incubation with histamine prior to challenge with poly I:C resulted in a significant increase of TSLP production compared to stimulation with poly I:C alone. Experiments with different histamine receptor agonists (H1R: 2-pyridylethylamine; H2R: amthamine; H2R/H4R: 4-methylhistamine (4MH)) revealed a dominant role for the H4R receptor, as 4-MH in combination with poly I:C displayed a significant increase of TSLP secretion, while the other agonists did not show any effect. The increase in TSLP production by 4MH was blocked with the H4R antagonist JNJ7777120. This effect was reproducible also in the murine KC cell line MSC. Taken together, our study indicates a new role for the H4 receptor in the regulation of TSLP in keratinocytes. Therefore, blocking of the H4R receptor in allergic diseases might be promising to alleviate inflammation and pruritus via TSLP. Copyright © 2016. Published by Elsevier Ltd.

  12. Directed plant cell-wall accumulation of iron: embedding co-catalyst for efficient biomass conversion.

    Science.gov (United States)

    Lin, Chien-Yuan; Jakes, Joseph E; Donohoe, Bryon S; Ciesielski, Peter N; Yang, Haibing; Gleber, Sophie-Charlotte; Vogt, Stefan; Ding, Shi-You; Peer, Wendy A; Murphy, Angus S; McCann, Maureen C; Himmel, Michael E; Tucker, Melvin P; Wei, Hui

    2016-01-01

    Plant lignocellulosic biomass is an abundant, renewable feedstock for the production of biobased fuels and chemicals. Previously, we showed that iron can act as a co-catalyst to improve the deconstruction of lignocellulosic biomass. However, directly adding iron catalysts into biomass prior to pretreatment is diffusion limited, and increases the cost of biorefinery operations. Recently, we developed a new strategy for expressing iron-storage protein ferritin intracellularly to accumulate iron as a catalyst for the downstream deconstruction of lignocellulosic biomass. In this study, we extend this approach by fusing the heterologous ferritin gene with a signal peptide for secretion into Arabidopsis cell walls (referred to here as FerEX). The transgenic Arabidopsis plants. FerEX. accumulated iron under both normal and iron-fertilized growth conditions; under the latter (iron-fertilized) condition, FerEX transgenic plants showed an increase in plant height and dry weight by 12 and 18 %, respectively, compared with the empty vector control plants. The SDS- and native-PAGE separation of cell-wall protein extracts followed by Western blot analyses confirmed the extracellular expression of ferritin in FerEX plants. Meanwhile, Perls' Prussian blue staining and X-ray fluorescence microscopy (XFM) maps revealed iron depositions in both the secondary and compound middle lamellae cell-wall layers, as well as in some of the corner compound middle lamella in FerEX. Remarkably, their harvested biomasses showed enhanced pretreatability and digestibility, releasing, respectively, 21 % more glucose and 34 % more xylose than the empty vector control plants. These values are significantly higher than those of our recently obtained ferritin intracellularly expressed plants. This study demonstrated that extracellular expression of ferritin in Arabidopsis can produce plants with increased growth and iron accumulation, and reduced thermal and enzymatic recalcitrance. The results are

  13. Lutein improves cell viability and reduces Alu RNA accumulation in hydrogen peroxide challenged retinal pigment epithelial cells.

    Science.gov (United States)

    Chong, You Sheng; Mai, Chun Wai; Leong, Chee Onn; Wong, Lai Chun

    2018-03-01

    Dysfunction of the microRNA (miRNA)-processing enzyme DICER1 and Alu RNA accumulation are linked to the pathogenesis of age-related macular degeneration (AMD). This study determined the optimal dose of lutein (LUT) and zeaxanthin (ZEA) to protect human retinal pigment epithelium (RPE) cells against hydrogen peroxide (H 2 O 2 ). The effect of the optimal dose of LUT and ZEA as DICER1 and Alu RNA modulators in cultured human RPE cells challenged with H 2 O 2 was investigated. ARPE-19 cells were pre-treated with LUT, ZEA, or both for 24 h before 200 μM H 2 O 2 challenge. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. DICER1 and Alu RNA were quantified by western blotting and real-time polymerase chain reaction, respectively. H 2 O 2 increased cell Alu RNA expression and decreased cell viability of ARPE-19, but had no significant impact on the DICER1 protein level. LUT, alone and in combination with ZEA pre-treatment, prior to H 2 O 2 challenge significantly improved cell viability of ARPE-19 and reduced the level of Alu RNA compared to the negative control. These results support the use of LUT alone, and in combination with ZEA, in AMD prevention and treatment. This study is also the first to report LUT modulating effects on Alu RNA.

  14. Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells

    International Nuclear Information System (INIS)

    Askmyr, M; Ågerstam, H; Lilljebjörn, H; Hansen, N; Karlsson, C; Palffy, S von; Landberg, N; Högberg, C; Lassen, C; Rissler, M; Richter, J; Ehinger, M; Järås, M; Fioretos, T

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34 + cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML

  15. Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of juvenile polyps.

    Science.gov (United States)

    Iwamoto, Michiko; Hoffenberg, Edward J; Carethers, John M; Doctolero, Ryan; Tajima, Akihiro; Sugano, Kentaro; Franklin, Wilbur A; Ahnen, Dennis J

    2005-01-01

    In the two conditions juvenile polyps (JPs) and juvenile polyposis coli (JPC), colonic polyps may have overlapping histologic and phenotypic appearance, but JPC confers a significant risk for colon adenocarcinoma. Although not thought to contain adenomatous polyposis coli (APC) mutations, the status of beta-catenin and full-length APC protein expression in JPs is not known. We evaluated beta-catenin and full-length APC protein expression in JPs from children with JPs and JPC. Cases were identified through endoscopic procedure records. Immunohistochemistry was performed for beta-catenin and full-length APC protein. Loss of heterozygosity at the APC gene locus on chromosome 5 was assessed using two APC-linked microsatellite markers. Polyp and normal colonic tissue were analyzed from 36 children with JPs and 9 with JPC. Both APC and beta-catenin immunoreactivity were present in epithelial cells from all samples but in different patterns. In all normal colon and polyp samples, APC expression was cytoplasmic with maximal immunoreactivity in the goblet cells. In contrast, beta-catenin immunoreactivity in epithelial cells was limited to the plasma membrane in normal colon but was both cytoplasmic and nuclear in all 45 JPs. No evidence of APC gene loss of heterozygosity was found. In polyps from children with JPs and JPC, nuclear beta-catenin accumulation is a consistent feature, and it is not due to APC gene mutation or loss of full-length APC protein expression. Thus, beta-catenin accumulation may be intrinsic to the formation of juvenile-type polyps through an as-yet-undefined mechanism.

  16. Brain histamine H1- and H2-receptors and histamine-sensitive adenylate cyclase: effects of antipsychotics and antidepressants

    International Nuclear Information System (INIS)

    Coupet, J.; Szuches-Myers, V.A.

    1981-01-01

    Several classes of psychoactive compounds have been investigated for their effects on histamine-sensitive adenylate cyclase in cell-free preparations from the guinea-pig cerebral cortex. Their inhibitory actions on this enzyme system have been compared with their abilities to displace [ 3 H]pyrilamine and [ 3 H]cimetidine from histamine H 1 - and H 2 -receptor sites, respectively. The results of these studies show that compounds which inhibited the histamine-sensitive cyclase were also displacers of either [ 3 H]pyrilamine or [ 3 H]cimetidine or both 3 H-ligands from their binding sites. In spite of the lack of a correlation between binding and cyclase antagonism it was observed that compounds that displace both ligands showed greater inhibition of the cyclase than those that have affinities for sites labeled by one or the other ligand. It was concluded that antihistamines, the antipsychotics and the antidepressants share a common property through their antagonism of H 1 -receptors and that may be responsible for their sedative side effect. (Auth.)

  17. Collagen Accumulation in Osteosarcoma Cells lacking GLT25D1 Collagen Galactosyltransferase*

    Science.gov (United States)

    Baumann, Stephan

    2016-01-01

    Collagen is post-translationally modified by prolyl and lysyl hydroxylation and subsequently by glycosylation of hydroxylysine. Despite the widespread occurrence of the glycan structure Glc(α1–2)Gal linked to hydroxylysine in animals, the functional significance of collagen glycosylation remains elusive. To address the role of glycosylation in collagen expression, folding, and secretion, we used the CRISPR/Cas9 system to inactivate the collagen galactosyltransferase GLT25D1 and GLT25D2 genes in osteosarcoma cells. Loss of GLT25D1 led to increased expression and intracellular accumulation of collagen type I, whereas loss of GLT25D2 had no effect on collagen secretion. Inactivation of the GLT25D1 gene resulted in a compensatory induction of GLT25D2 expression. Loss of GLT25D1 decreased collagen glycosylation by up to 60% but did not alter collagen folding and thermal stability. Whereas cells harboring individually inactivated GLT25D1 and GLT25D2 genes could be recovered and maintained in culture, cell clones with simultaneously inactive GLT25D1 and GLT25D2 genes could be not grown and studied, suggesting that a complete loss of collagen glycosylation impairs osteosarcoma cell proliferation and viability. PMID:27402836

  18. Weight Cycling Increases T-Cell Accumulation in Adipose Tissue and Impairs Systemic Glucose Tolerance

    Science.gov (United States)

    Anderson, Emily K.; Gutierrez, Dario A.; Kennedy, Arion; Hasty, Alyssa H.

    2013-01-01

    Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential correlation are not known. For determination of whether weight cycling modulates AT immune cell populations, inflammation, and insulin resistance, mice were subjected to a diet-switch protocol designed to induce weight cycling. Weight-cycled mice displayed decreased systemic glucose tolerance and impaired AT insulin sensitivity when compared with mice that gained weight but did not cycle. AT macrophage number and polarization were not modulated by weight cycling. However, weight cycling did increase the number of CD4+ and CD8+ T cells in AT. Expression of multiple T helper 1–associated cytokines was also elevated subsequent to weight cycling. Additionally, CD8+ effector memory T cells were present in AT of both obese and weight-cycled mice. These studies indicate that an exaggerated adaptive immune response in AT may contribute to metabolic dysfunction during weight cycling. PMID:23733197

  19. Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis

    Science.gov (United States)

    Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C.; Yang, Xiangdong; Ge, Junbo

    2015-01-01

    Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b+Gr-1+ immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC−/−) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b+Gr-1+ IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration. PMID:26278136

  20. Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.

    Science.gov (United States)

    Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C; Yang, Xiangdong; Ge, Junbo

    2015-08-17

    Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.

  1. From Accumulation to Degradation: Reprogramming Polyamine Metabolism Facilitates Dark-Induced Senescence in Barley Leaf Cells.

    Science.gov (United States)

    Sobieszczuk-Nowicka, Ewa; Kubala, Szymon; Zmienko, Agnieszka; Małecka, Arleta; Legocka, Jolanta

    2015-01-01

    The aim of this study was to analyze whether polyamine (PA) metabolism is involved in dark-induced Hordeum vulgare L. 'Nagrad' leaf senescence. In the cell, the titer of PAs is relatively constant and is carefully controlled. Senescence-dependent increases in the titer of the free PAs putrescine, spermidine, and spermine occurred when the process was induced, accompanied by the formation of putrescine conjugates. The addition of the anti-senescing agent cytokinin, which delays senescence, to dark-incubated leaves slowed the senescence-dependent PA accumulation. A feature of the senescence process was initial accumulation of PAs at the beginning of the process and their subsequent decrease during the later stages. Indeed, the process was accompanied by both enhanced expression of PA biosynthesis and catabolism genes and an increase in the activity of enzymes involved in the two metabolic pathways. To confirm whether the capacity of the plant to control senescence might be linked to PA, chlorophyll fluorescence parameters, and leaf nitrogen status in senescing barley leaves were measured after PA catabolism inhibition and exogenously applied γ-aminobutyric acid (GABA). The results obtained by blocking putrescine oxidation showed that the senescence process was accelerated. However, when the inhibitor was applied together with GABA, senescence continued without disruption. On the other hand, inhibition of spermidine and spermine oxidation delayed the process. It could be concluded that in dark-induced leaf senescence, the initial accumulation of PAs leads to facilitating their catabolism. Putrescine supports senescence through GABA production and spermidine/spermine supports senescence-dependent degradation processes, is verified by H2O2 generation.

  2. In Silico Modeling of Liver Metabolism in a Human Disease Reveals a Key Enzyme for Histidine and Histamine Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Pagliarini

    2016-06-01

    Full Text Available Primary hyperoxaluria type I (PH1 is an autosomal-recessive inborn error of liver metabolism caused by alanine:glyoxylate aminotransferase (AGT deficiency. In silico modeling of liver metabolism in PH1 recapitulated accumulation of known biomarkers as well as alteration of histidine and histamine levels, which we confirmed in vitro, in vivo, and in PH1 patients. AGT-deficient mice showed decreased vascular permeability, a readout of in vivo histamine activity. Histamine reduction is most likely caused by increased catabolism of the histamine precursor histidine, triggered by rerouting of alanine flux from AGT to the glutamic-pyruvate transaminase (GPT, also known as the alanine-transaminase ALT. Alanine administration reduces histamine levels in wild-type mice, while overexpression of GPT in PH1 mice increases plasma histidine, normalizes histamine levels, restores vascular permeability, and decreases urinary oxalate levels. Our work demonstrates that genome-scale metabolic models are clinically relevant and can link genotype to phenotype in metabolic disorders.

  3. Lesional accumulation of CD163-expressing cells in the gut of patients with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Eleonora Franzè

    Full Text Available Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD, but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response.

  4. Intercellular K⁺ accumulation depolarizes Type I vestibular hair cells and their associated afferent nerve calyx.

    Science.gov (United States)

    Contini, D; Zampini, V; Tavazzani, E; Magistretti, J; Russo, G; Prigioni, I; Masetto, S

    2012-12-27

    Mammalian vestibular organs contain two types of sensory receptors, named Type I and Type II hair cells. While Type II hair cells are contacted by several small afferent nerve terminals, the basolateral surface of Type I hair cells is almost entirely enveloped by a single large afferent nerve terminal, called calyx. Moreover Type I, but not Type II hair cells, express a low-voltage-activated outward K(+) current, I(K,L), which is responsible for their much lower input resistance (Rm) at rest as compared to Type II hair cells. The functional meaning of I(K,L) and associated calyx is still enigmatic. By combining the patch-clamp whole-cell technique with the mouse whole crista preparation, we have recorded the current- and voltage responses of in situ hair cells. Outward K(+) current activation resulted in K(+) accumulation around Type I hair cells, since it induced a rightward shift of the K(+) reversal potential the magnitude of which depended on the amplitude and duration of K(+) current flow. Since this phenomenon was never observed for Type II hair cells, we ascribed it to the presence of a residual calyx limiting K(+) efflux from the synaptic cleft. Intercellular K(+) accumulation added a slow (τ>100ms) depolarizing component to the cell voltage response. In a few cases we were able to record from the calyx and found evidence for intercellular K(+) accumulation as well. The resulting depolarization could trigger a discharge of action potentials in the afferent nerve fiber. Present results support a model where pre- and postsynaptic depolarization produced by intercellular K(+) accumulation cooperates with neurotransmitter exocytosis in sustaining afferent transmission arising from Type I hair cells. While vesicular transmission together with the low Rm of Type I hair cells appears best suited for signaling fast head movements, depolarization produced by intercellular K(+) accumulation could enhance signal transmission during slow head movements. Copyright

  5. Role of histamine in the regulation of intestinal immunity in fish.

    Science.gov (United States)

    Galindo-Villegas, Jorge; Garcia-Garcia, Erick; Mulero, Victoriano

    2016-11-01

    In mammals, during the acute inflammatory response, the complex interrelationship and cross-talk among histamine and the immune system has been fairly well characterized. There is a substantial body of information on its structure, metabolism, receptors, signal transduction, physiologic and pathologic effects. However, for early vertebrates, there is little such knowledge. In the case of teleost fish, this lack of knowledge has been due to the widely held belief that histamine is not present in this phylogenetic group. However, it has been recently demonstrated, that granules of mast cells in perciforms contain biologically active histamine. More importantly, the inflammatory response was clearly demonstrated to be regulated by the direct action of histamine on professional phagocytes. Nevertheless, the molecular basis and exact role of this biogenic amine in perciforms is still a matter of speculation. Therefore, this review intends to summarize recent experimental evidence regarding fish mast cells and correlate the same with their mammalian counterparts to establish the possible role of histamine in the fish intestinal inflammatory response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

    Directory of Open Access Journals (Sweden)

    Paris Jafari

    Full Text Available Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i 3-OHGA causes the death of astrocytes, (ii deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

  7. Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs

    DEFF Research Database (Denmark)

    Birck, Malene Muusfeldt; Saraste, Antti; Hyttel, Poul

    2013-01-01

    Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia...

  8. In vivo comparative immunotoxic study of histamine receptors (H1R, H2R, H3R and H4R)-agonist

    OpenAIRE

    Tripathi, Trivendra; Shahid, Mohammad; Raza, Adil; Khan, Haris M.; Siddiqui, Mashiatullah; Malik, Abida; Khan, Rahat Ali

    2013-01-01

    Abstract. Accumulating evidences have highlighted histamine and histamine receptors (HRs)-antagonists’ role in immunomodulation. However, the roles of HRs-agonists are still unclear. The present study was therefore designed to delineate the comparative immunotoxic roles of H1-H4-agonist on antibody generation profile in rabbit model. The cohort comprised of seven groups (Group-I negative control, group-II positive control and group-III-VII HRs-agonist-treated) containing 18 (9 male and 9 fema...

  9. Influence of nimodipine, verapamil and lanthanum on histamine release from human basophils

    DEFF Research Database (Denmark)

    Jensen, C B; Thastrup, Ole; Norn, S

    1987-01-01

    and the calcium channels, using the calcium antagonists nimodipine, verapamil and lanthanum. Anti-IgE-induced histamine release was inhibited by verapamil, nimodipine and lanthanum. When cells were pretreated with sialidase in order to remove sialic acid from the cell membrane, the inhibitory action of nimodipine...... was abolished, whereas the inhibition by verapamil or lanthanum was unaffected. This difference may be explained by the different mode of action of the calcium channel antagonists, and the results suggest an association between membrane sialic acid and the calcium channel.......Our previous studies suggest that the membrane content of sialic acid influences histamine release from human basophils by interfering with the transmembraneous calcium fluxes preceding histamine release. In this study we investigated a possible interaction between membrane sialic acid...

  10. Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

    Science.gov (United States)

    Thomas, Carissa M.; Hong, Teresa; van Pijkeren, Jan Peter; Hemarajata, Peera; Trinh, Dan V.; Hu, Weidong; Britton, Robert A.; Kalkum, Markus; Versalovic, James

    2012-01-01

    Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases. PMID:22384111

  11. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.

    Directory of Open Access Journals (Sweden)

    Carissa M Thomas

    Full Text Available Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA, histidine/histamine antiporter (hdcP, and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H(2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.

  12. Uptake of Gold Nanoparticles by Intestinal Epithelial Cells: Impact of Particle Size on Their Absorption, Accumulation, and Toxicity.

    Science.gov (United States)

    Yao, Mingfei; He, Lili; McClements, David Julian; Xiao, Hang

    2015-09-16

    Inorganic nanomaterials have been increasingly utilized in many consumer products, which has led to concerns about their potential toxicity. At present, there is limited knowledge about the gastrointestinal fate and cytotoxicity of ingested inorganic nanoparticles. This study determined the influence of particle size and concentration of gold nanoparticles (AuNPs) on their absorption, accumulation, and cytotoxicity in model intestinal epithelial cells. As the mean particle diameter of the AuNPs decreased (from 100 to 50 to 15 nm), their rate of absorption by the intestinal epithelium cells increased, but their cellular accumulation in the epithelial cells decreased. Moreover, accumulation of AuNPs caused cytotoxicity in the intestinal epithelial cells, which was evidenced by depolarization of mitochondria membranes. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity.

  13. Model of Organic Solar Cell Photocurrent Including the Effect of Charge Accumulation at Interfaces and Non-Uniform Carrier Generation

    DEFF Research Database (Denmark)

    Torto, Lorenzo; Cester, Andrea; Rizzo, Antonio

    2017-01-01

    We developed an improved model to fit the photocurrent density versus voltage in organic solar cells. The model has been validated by fitting data from P3HT:PCBM solar cells. Our model quantitatively accounts for the band bending near the electrodes caused by charge accumulation in the active layer...

  14. Accumulation of bioactive lipids during storage of blood products is not cell but plasma derived and temperature dependent

    NARCIS (Netherlands)

    Vlaar, Alexander P. J.; Kulik, Wim; Nieuwland, Rienk; Peters, Charlotte P.; Tool, Anton T. J.; van Bruggen, Robin; Juffermans, Nicole P.; de Korte, Dirk

    2011-01-01

    Bioactive lipids (lysophosphatidylcholines [lysoPCs]) accumulating during storage of cell-containing blood products are thought to be causative in onset of transfusion-related acute lung injury through activation of neutrophils. LysoPCs are thought to be derived from cell membrane degradation

  15. Accumulation of 3-hydroxytetradecenoic acid: Cause or corollary of glucolipotoxic impairment of pancreatic β-cell bioenergetics?

    Directory of Open Access Journals (Sweden)

    Nicolai M. Doliba

    2015-12-01

    Conclusions: As long chain 3-hydroxylated FA metabolites are known to uncouple heart and brain mitochondria [53–55], we propose that under glucolipotoxic condition, unsaturated hydroxylated long-chain FAs accumulate, uncouple and ultimately inhibit β-cell respiration. This leads to the slow deterioration of mitochondrial function progressing to bioenergetics β-cell failure.

  16. Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Ji Hye Park

    2016-10-01

    Full Text Available Doxorubicin (DOXO is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs. DOXO induced hCPC apoptosis with reduction of SMP30 (regucalcin and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin and CaMKII (Calmodulin kinase II. The results of an LC3 puncta assay further indicated that DOXO reduced autophagosome formation via accumulation of cytosolic Ca2+. Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus, DOXO-mediated hCPC toxicity is linked to Ca2+-related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against DOXO-mediated hCPC toxicity.

  17. Auxin efflux carrier activity and auxin accumulation regulate cell division and polarity in tobacco cells

    Czech Academy of Sciences Publication Activity Database

    Petrášek, Jan; Elčkner, Miroslav; Morris, David; Zažímalová, Eva

    2002-01-01

    Roč. 216, - (2002), s. 302-308 ISSN 0032-0935 R&D Projects: GA ČR GA206/98/1510 Grant - others:INCO Copernicus(BE) IC15-CT98-0118 Institutional research plan: CEZ:AV0Z5038910 Keywords : Auxin carrier * 1,N,Naphthylphthalamic acid * Nicotiana ( cell culture) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.960, year: 2002

  18. Discovery of a novel, monocationic, small-molecule inhibitor of scrapie prion accumulation in cultured sheep microglia and Rov cells.

    Science.gov (United States)

    Stanton, James B; Schneider, David A; Dinkel, Kelcey D; Balmer, Bethany F; Baszler, Timothy V; Mathison, Bruce A; Boykin, David W; Kumar, Arvind

    2012-01-01

    Prion diseases, including sheep scrapie, are neurodegenerative diseases with the fundamental pathogenesis involving conversion of normal cellular prion protein (PrP(C)) to disease-associated prion protein (PrP(Sc)). Chemical inhibition of prion accumulation is widely investigated, often using rodent-adapted prion cell culture models. Using a PrP(Sc)-specific ELISA we discovered a monocationic phenyl-furan-benzimidazole (DB772), which has previously demonstrated anti-pestiviral activity and represents a chemical category previously untested for anti-prion activity, that inhibited PrP(Sc) accumulation and prion infectivity in primary sheep microglial cell cultures (PRNP 136VV/154RR/171QQ) and Rov9 cultures (VRQ-ovinized RK13 cells). We investigated potential mechanisms of this anti-prion activity by evaluating PrP(C) expression with quantitative RT-PCR and PrP ELISA, comparing the concentration-dependent anti-prion and anti-pestiviral effects of DB772, and determining the selectivity index. Results demonstrate at least an approximate two-log inhibition of PrP(Sc) accumulation in the two cell systems and confirmed that the inhibition of PrP(Sc) accumulation correlates with inhibition of prion infectivity. PRNP transcripts and total PrP protein concentrations within cell lysates were not decreased; thus, decreased PrP(C) expression is not the mechanism of PrP(Sc) inhibition. PrP(Sc) accumulation was multiple logs more resistant than pestivirus to DB772, suggesting that the anti-PrP(Sc) activity was independent of anti-pestivirus activity. The anti-PrP(Sc) selectivity index in cell culture was approximately 4.6 in microglia and 5.5 in Rov9 cells. The results describe a new chemical category that inhibits ovine PrP(Sc) accumulation in primary sheep microglia and Rov9 cells, and can be used for future studies into the treatment and mechanism of prion diseases.

  19. Association of myasthenia gravis with polymorphisms in the gene of histamine N-methyltransferase

    DEFF Research Database (Denmark)

    Kellermayer, Blanka; Polgar, Noemi; Pal, Jozsef

    2013-01-01

    Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine. Histamine modulates immune responses and plays a role in the pathogenesis of autoimmune disorders.......Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine. Histamine modulates immune responses and plays a role in the pathogenesis of autoimmune disorders....

  20. Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease

    OpenAIRE

    Batta, Gyula; Soltész, Lilla; Kovács, Tamás; Bozó, Tamás; Mészár, Zoltán; Kellermayer, Miklós; Szöllősi, János; Nagy, Peter

    2018-01-01

    Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accom...

  1. Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock.

    Science.gov (United States)

    Kim, Yoon Sik; Kim, Young-Beom; Kim, Woong Bin; Lee, Seung Won; Oh, Seog Bae; Han, Hee-Chul; Lee, C Justin; Colwell, Christopher S; Kim, Yang In

    2016-05-06

    Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca(2+) concentration ([Ca(2+)]i) through the activation of CaV1.3 L-type Ca(2+) channels and Ca(2+)-induced Ca(2+) release from ryanodine receptor-mediated internal stores. In the current study, we explored the underlying mechanisms with various techniques including Ca(2+)- and Cl(-)-imaging and extracellular single-unit recording. Our hypothesis was that histamine causes Cl(-) efflux through cystic fibrosis transmembrane conductance regulator (CFTR) to elicit membrane depolarization needed for the activation of CaV1.3 Ca(2+) channels in SCN neurons. We found that histamine elicited Cl(-) efflux and increased [Ca(2+)]i in dissociated mouse SCN cells. Both of these events were suppressed by bumetanide [Na(+)-K(+)-2Cl(-) cotransporter isotype 1 (NKCC1) blocker], CFTRinh-172 (CFTR inhibitor), gallein (Gβγ protein inhibitor) and H89 [protein kinase A (PKA) inhibitor]. By itself, H1R activation with 2-pyridylethylamine increased the level of cAMP in the SCN and this regulation was prevented by gallein. Finally, histamine-evoked phase shifts of the circadian neural activity rhythm in the mouse SCN slice were blocked by bumetanide, CFTRinh-172, gallein or H89 and were not observed in NKCC1 or CFTR KO mice. Taken together, these results indicate that histamine recruits the H1R-Gβγ-cAMP/PKA pathway in the SCN neurons to activate CaV1.3 channels through CFTR-mediated Cl(-) efflux and ultimately to phase-shift the circadian clock. This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system.

  2. Histamine Clearance Through Polyspecific Transporters in the Brain.

    Science.gov (United States)

    Yoshikawa, Takeo; Yanai, Kazuhiko

    2017-01-01

    Histamine plays an important role as a neurotransmitter in diverse brain functions, and clearance of histamine is essential to avoid excessive histaminergic neuronal activity. Histamine N-methyltransferase, which is an enzyme in the central nervous system that metabolizes histamine, is localized to the cytosol. This suggests that a histamine transport process is essential to inactivate histamine. Previous reports have shown the importance of astrocytes for histamine transport, although neuronal histamine transport could not be ruled out. High-affinity and selective histamine transporters have not yet been discovered, although it has been reported that the following three polyspecific transporters transport histamine: organic cation transporter (OCT) 2, OCT3, and plasma membrane monoamine transporter (PMAT). The K m values of human OCT2, OCT3, and PMAT are 0.54, 0.64, and 4.4 mM, respectively. The three transporters are expressed in the brain, and their regional distribution is different. Recent studies revealed the contribution of OCT3 and PMAT to histamine transport by primary human astrocytes. Several investigations using mice supported the importance of OCT3 for histamine clearance in the brain. However, further studies are required to elucidate the detailed mechanism of histamine transport in the brain.

  3. The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

    Directory of Open Access Journals (Sweden)

    Katarina Radulovic

    Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

  4. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    International Nuclear Information System (INIS)

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-01-01

    levels of the basal transcription factor TATA-binding protein (TBP) and global transcription, and severely limited cell growth. Expression of a prelamin A variant that cannot be farnesylated, although did not appreciably influence cell growth, resulted in the formation of lamin A nucleoplasmic foci and caused, in a minor subpopulation of cells, changes in nuclear morphology that were accompanied by reduced levels of TBP and transcription. In contrast, expression of mature lamin A did not affect any of these parameters. These data demonstrate that accumulation of any partially processed prelamin A protein alters cellular homeostasis to some degree, even though the most dramatic effects are caused by variants with a permanently farnesylated carboxyl-terminal tail.

  5. The role for human nasal epithelial nuclear factor kappa B activation in histamine-induced mucin 5 subtype B overproduction.

    Science.gov (United States)

    Wang, Weiwei; Shao, Shengwen; Wang, Sha

    2016-03-01

    Mucin 5 subtype B (MUC5B) is 1 of the major mucins secreted by airway epithelial cells. We sought to determine the effect of histamine on MUC5B expression in human nasal epithelial cells. Human nasal epithelial cells from allergic rhinitis patients were cultured, and stimulated with 4 concentrations of histamine, or pretreated with a specific nuclear factor-kappa B (NF-κB) inhibitor (Bay11-7082) before histamine stimulation. Immunocytochemistry and Western blotting were used to detect phosphorylated inhibitor of kappa B alpha (p-IκBα), NF-κBp65 and MUC5B protein. MUC5B content in supernatants was assayed by enzyme-linked immunosorbent assay (ELISA). Histamine promoted IκBα phosphorylation and NF-κBp65 nuclear translocation. A concentration-dependent histamine-induced increase of MUC5B protein was observed, and its content in supernatants was upregulated in a concentration-dependent fashion, but these effects were attenuated by Bay11-7082. Histamine activated the IκBα/NF-κB pathway by promoting IκBα phosphorylation and inducing NF-κBp65 nuclear translocation, contributing to MUC5B overproduction and secretion. © 2015 ARS-AAOA, LLC.

  6. Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell–cell recognition and fusion

    Science.gov (United States)

    Weichert, Martin; Lichius, Alexander; Priegnitz, Bert-Ewald; Brandt, Ulrike; Gottschalk, Johannes; Nawrath, Thorben; Groenhagen, Ulrike; Read, Nick D.; Schulz, Stefan; Fleißner, André

    2016-01-01

    Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell–cell communication and fusion in the fungus Neurospora crassa. Genetically identical germinating spores of this fungus undergo cell–cell fusion, thereby forming a highly interconnected supracellular network during colony initiation. Before fusion, the cells use an unusual signaling mechanism that involves the coordinated and alternating switching between signal sending and receiving states of the two fusion partners. Accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain disrupts this coordinated cell–cell communication and suppresses cell fusion. These specific sterol precursors target a single ERK-like mitogen-activated protein (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK-2), which is also involved in cell fusion, is unaffected. These observations indicate that a minor specific change in sterol structure can exert a strong detrimental effect on a key signaling pathway of the cell, resulting in the absence of cell fusion. PMID:27708165

  7. Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

    DEFF Research Database (Denmark)

    Platzer, M H; Grattan, C E H; Poulsen, Lars K.

    2005-01-01

    Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immuno......Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against...... the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients...

  8. CXCL13 promotes isotype-switched B cell accumulation to the central nervous system during viral encephalomyelitis.

    Science.gov (United States)

    Phares, Timothy W; DiSano, Krista D; Stohlman, Stephen A; Segal, Benjamin M; Bergmann, Cornelia C

    2016-05-01

    Elevated CXCL13 within the central nervous system (CNS) correlates with humoral responses in several neuroinflammatory diseases, yet its role is controversial. During coronavirus encephalomyelitis CXCL13 deficiency impaired CNS accumulation of memory B cells and antibody-secreting cells (ASC) but not naïve/early-activated B cells. However, despite diminished germinal center B cells and follicular helper T cells in draining lymph nodes, ASC in bone marrow and antiviral serum antibody were intact in the absence of CXCL13. The data demonstrate that CXCL13 is not essential in mounting effective peripheral humoral responses, but specifically promotes CNS accumulation of differentiated B cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. ENERGY-DEPENDENT PROCESSES INVOLVED IN REDUCED DRUG ACCUMULATION IN MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINES WITHOUT P-GLYCOPROTEIN EXPRESSION

    NARCIS (Netherlands)

    VERSANTVOORT, CHM; BROXTERMAN, HJ; PINEDO, HM; DEVRIES, EGE; FELLER, N; KUIPER, CM; LANKELMA, J

    1992-01-01

    Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/ 2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of

  10. Effects of bepotastine and fexofenadine on histamine-induced flare, wheal and itch.

    Science.gov (United States)

    Tanizaki, Hideaki; Ikoma, Akihiko; Fukuoka, Miyuki; Miyachi, Yoshiki; Kabashima, Kenji

    2012-01-01

    Urticaria is mainly caused by mast cell-derived histamine through the histamine H(1) receptor. Antihis