Genistein suppresses psoriasis-related inflammation through a STAT3-NF-κB-dependent mechanism in keratinocytes.

Abstract

Psoriasis is a chronic recurrent skin inflammatory disease, and inhibition of inflammation may be an effective means of treating psoriasis. The flavonoid genistein has a clear anti-inflammatory effect. However, the anti-psoriatic effects of genistein and their underlying mechanisms remain unclear. In this study, we investigated the effects of genistein on imiquimod (IMQ)-induced psoriasis-like skin lesions in vivo and explored the mechanisms underlying those effects in vitro. It was found that genistein can significantly improve IMQ-induced pathological scores of cutaneous skin lesions in mice, reduce epidermal thickness, and inhibit the expression of inflammatory factors，including interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), IL-17 and IL-23. In vitro studies, genistein inhibited the proliferation of human keratinocyte HaCaT cells and inhibited the expression of inflammatory factors in a dose-dependent manner which induced by TNFα. Further researches showed that genistein could also significantly inhibit phosphorylated STAT3 (pSAT3) expression in IMQ mice dorsal skin and in TNF-α-induced HaCaT cells. The inhibitory effect of genistein on the expression of IL-6, IL-23 and TNF-α was weakened after Stat3 siRNA in HaCaT cells. Genistein could also significantly inhibit TNF-α induced the nuclear translocation of NF-κB, and inhibit the phosphorylation of I-kBα (pI-kBα). After combining with NF-κB blocker BAY 11-7082, the effect of genistein down-regulate the expression of TNF-α and VEGFA was attenuated in HaCaT cells. The results suggest that genistein may be developed for the treatment of psoriasis lesions.

• Authors: Ailin Wang, Jianan Wei, Chuanjian Lu, Haiming Chen, Xiaoqin Zhong, Yue Lu, Leng Li, Haiding Huang, Zhenhua Dai, Ling Han
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 69 Pg. 270-278 (Apr 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30743203 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• NF-kappa B
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Vascular Endothelial Growth Factor A
• siroamide
• vascular endothelial growth factor A, mouse
• Heme
• Genistein
• Imiquimod

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cell Line
• Cytokines (metabolism)
• Disease Models, Animal
• Genistein (therapeutic use)
• Heme (analogs & derivatives)
• Humans
• Imiquimod
• Inflammation Mediators (metabolism)
• Keratinocytes (drug effects, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• NF-kappa B (metabolism)
• Psoriasis (drug therapy)
• STAT3 Transcription Factor (genetics, metabolism)
• Vascular Endothelial Growth Factor A (metabolism)