title: Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells.
abstract: Upregulation of pro-inflammatory mediators contributes to β-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic β-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-γ. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine- induced signaling cascades leading to nuclear factor kappa B (NF-κB) activation, including IκB-kinase (IKK) activation, IκB degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-κB in RINm5F cells.
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors: Sung Mi
authors: SM
authors: Ju
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors: Gi Soo
authors: GS
authors: Youn
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors: Yoon Shin
authors: YS
authors: Cho
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors: Soo Young
authors: SY
authors: Choi
authors: Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors: Jinseu
authors: J
authors: Park
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000633:toxicity*; D018836:Inflammation Mediators / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D053978:Pentacyclic Triterpenes; D051381:Rats; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C050414:celastrol