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KMID : 0624620150480030172
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BMB Reports
2015 Volume.48 No. 3 p.172 ~ p.177
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Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells
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Ju Sung-Mi
Youn Gi-Soo
Cho Yoon-Shin
Choi Soo-Young
Park Jin-Seu
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Abstract
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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 I?B-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.
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KEYWORD
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β-cell, Celastrol, Cytokine, Inflammation, NF-κB
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