DEFF Research Database (Denmark)

Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC damage and disturbance of the epithelial integrity.

Energy Technology Data Exchange (ETDEWEB)

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of {sup 3}H from ({sup 3}H)tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal ...

International Nuclear Information System (INIS)

The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-#alpha# antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-#alpha# antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI ...

British Library Electronic Table of Contents (United Kingdom)

Tumour necrosis factor-alpha (TNF-?) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-? antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-? antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5?mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0?4?mm) and 95 (52%) had a positive (?5?mm)...

Energy Technology Data Exchange (ETDEWEB)

Backgrund: Interleukin-1, tumornecrosisfactor-{alpha} and interferon-{gamma} endogenously provide protection of the hematopoietic system against radiation. Thiols have already been used successfully as radioprotective agents. In this study the effect von N-acetylcysteine (NAC) on the release of interleukin-1{alpha} and {beta} (IL-1), interleukin-2 (IL-2), interferon-{gamma} (IFN-{gamma}) and tumornecrosisfactor-{alpha} (TNF-{alpha}) was assessed in an in vitro assay. Patients and Methods: Whole blood samples from 8 healthy volunteers were stimulated with 7.5 {mu}m/ml PHA. NAC was added at concentrations of 0.6, 6, 12 and 24 mmol/l. Subsequently the samples were irradiated with a dose of 18 Gy according to preceding validation experiments. Results: IL-1{alpha}, IL-1{beta} and IL-2: In comparison to simulation and radiation alone the addition of 0.6 and 6 mmol/l with IL-2 also 12 mmol/l, NAC resulted in a significant increase of the cytokine-concentrations. The ...

UK PubMed Central (United Kingdom)

In recent years RNA interference (RNAi) has rapidly become the most widely used tool for gene knockdown due to its high specificity and potency. RNAi is an evolutionarily conserved mechanism...Full Text Available

UK PubMed Central (United Kingdom)

Some cases of autism spectrum disorder (ASD) have mutations in the lipid phosphatase, Pten (phosphatase and tensin homolog on chromosome 10). Tissue...Full Text Available

UK PubMed Central (United Kingdom)

Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development....Full Text Available

International Nuclear Information System (INIS)

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by TNF#alpha# and a set of ...

British Library Electronic Table of Contents (United Kingdom)

Recently, we cloned purpurin cDNA as an upregulated gene in the axotomized fish retina. The retina-specific protein was secreted from photoreceptors to ganglion cell layer during an early stage of optic nerve regeneration in zebrafish retina. The purpurin worked as a trigger molecule for axonal regrowth in adult injured fish retina. During zebrafish development, purpurin mRNA first appeared in ventral retina at 2 days post-fertilization (dpf) and spread out to the outer nuclear layer at 3 dpf. Here, we investigated the role of purpurin for zebrafish retinal development using morpholino gene knockdown technique. Injection of purpurin morpholino into the 1-2 cell stage of embryos significantly inhibited the transcriptional and translational expression of purpurin at 3 dpf. In the purpurin mo...

British Library Electronic Table of Contents (United Kingdom)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

British Library Electronic Table of Contents (United Kingdom)

Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...