1. Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A.
- Author
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Park, Aeri and Heo, Tae-Hwe
- Subjects
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AUTOPHAGY , *CELL populations , *T helper cells , *PLANT extracts , *SMALL molecules - Abstract
Anti-IL-17A antibodies, such as secukinumab and ixekizumab, are effective proinflammatory cytokine inhibitors for autoimmune disorders, including psoriasis. However, anti-IL-17A small molecule treatments are yet to be commercialized. Celastrol, a natural compound extracted from the roots of traditional Chinese medicinal plants, has anti-inflammatory and antioxidant properties. However, the binding of celastrol to IL-17A and the associated anti-inflammatory mechanisms remain unclear. This study investigated whether celastrol could directly bind to IL-17A and regulate inflammation in psoriatic in vitro and in vivo models. The results showed that celastrol directly binds to IL-17A and inhibits its downstream signaling, including the NF-kB and MAPK pathways. Interestingly, celastrol restored autophagy dysfunction and reduced proinflammatory cytokine secretion in keratinocytes. In addition, celastrol increased autophagy in the epidermis of a mouse model of psoriasis. Celastrol decreased Th17 cell populations and proinflammatory cytokine levels in mice. Thus, IL-17A-targeting celastrol reduced inflammation by rescuing impaired autophagy in in vitro and in vivo models of psoriasis, demonstrating its potential as a substitute for anti-IL-17A antibodies for treating psoriasis. • Celastrol binds directly to IL-17A, effectively blocking its signaling. • IL-17A-targeting celastrol restores autophagic reduction in IL-17A-keratinocytes and psoriatic mouse skin tissues. • IL-17A-targeting celastrol can help reduce inflammation in psoriasis by regulating autophagy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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