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Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A
1Laboratory of PharmacoImmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|February 17, 2024
Summary
Celastrol directly binds to Interleukin-17A (IL-17A), inhibiting inflammation in psoriasis models. This natural compound shows potential as a novel therapeutic by restoring autophagy and reducing inflammatory cytokines, offering an alternative to current antibody treatments.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Anti-interleukin-17A (IL-17A) antibodies are effective for autoimmune diseases like psoriasis.
- Small molecule inhibitors targeting IL-17A are not yet available.
- Celastrol, a natural compound, possesses anti-inflammatory properties, but its mechanism against IL-17A is unknown.
Purpose of the Study:
- To investigate if celastrol directly binds to IL-17A.
- To explore celastrol's anti-inflammatory mechanisms in psoriasis.
- To evaluate celastrol's therapeutic potential for psoriasis.
Main Methods:
- In vitro and in vivo psoriasis models were used.
- Celastrol's binding to IL-17A was assessed.
- Downstream signaling pathways (NF-kB, MAPK) and autophagy were analyzed.
- Cytokine levels and immune cell populations were measured.
Main Results:
- Celastrol directly binds to IL-17A, inhibiting NF-kB and MAPK signaling.
- Celastrol restored autophagy dysfunction in keratinocytes and psoriasis mouse models.
- Reduced secretion of pro-inflammatory cytokines and decreased Th17 cell populations were observed.
- Celastrol demonstrated efficacy in both in vitro and in vivo psoriasis models.
Conclusions:
- Celastrol directly targets IL-17A and modulates key inflammatory pathways.
- Celastrol's ability to rescue autophagy dysfunction is a key anti-inflammatory mechanism.
- Celastrol shows promise as a potential small molecule therapeutic for psoriasis, offering an alternative to anti-IL-17A antibodies.
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