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Celastrol regulates innate immunity response via NF‐kB and HSP70 in ARPE‐19 cells
Author(s) -
PAIMELA T
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.2132.x
Subject(s) - celastrol , hsp70 , lipopolysaccharide , nf κb , chemistry , inflammation , innate immune system , cytokine , microbiology and biotechnology , heat shock protein , immunology , biology , immune system , biochemistry , apoptosis , gene
Purpose Chronic inflammation participates in the pathology of age‐related macular degeneration (AMD). Recent studies indicate that celastrol, a novel triterpene compound, modulates inflammatory responses, but its effect on the human retinal pigment epithelial cells is poorly understood. In this study, we investigated the potential anti‐inflammatory role of celastrol and its effect on nuclear factor kappa B (NF‐kB) activity in human retinal pigment epithelial cells (ARPE‐19). Methods ARPE‐19 cells were exposed to lipopolysaccharide (LPS; TLR 4 agonist) with simultaneous exposure to various concentrations of celastrol and the secretion of IL‐6 cytokine was analyzed by ELISA. The effect of celastrol exposure on heat shock protein 70 (HSP70) expression was analyzed by western blotting. In response to celastrol and modulated HSP70 levels NF‐kB activity was examined by ELISA. Results Celastrol suppressed the LPS‐induced IL‐6 expression levels via NF‐kB transcription factor in ARPE‐19 cells. Celastrol evoked elevated HSP70 levels without cytotoxicity. Interestingly, celastrols capability to inhibit NF‐kB activity was diminished when HSP70 response was suppressed by siRNA. This reveals that celastrol has potent anti‐inflammatory capacity in ARPE‐19 cells, and its effect is modulated through NF‐kB and HSP70. Conclusion Our findings reveal that celastrol is a novel compound to suppress innate immunity response in human retinal pigment epithelial cells.