Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells

• Published in: BMB reports Vol. 48; no. 3; pp. 172 - 177
• Main Authors: Ju, Sung Mi, Youn, Gi Soo, Cho, Yoon Shin, Choi, Soo Young, Park, Jinseu
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.03.2015; 생화학분자생물학회
• Subjects: Animals; Cell Line; Chemokine CCL2 - metabolism; Cyclooxygenase 2 - metabolism; Cytokines - toxicity; Inflammation Mediators - toxicity; NF-kappa B - metabolism; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - antagonists & inhibitors; Rats; Triterpenes - pharmacology; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2015.48.3.147

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.