Taxifolin inhibits keratinocyte proliferation and ameliorates imiquimod-induced psoriasis-like mouse model via regulating cytoplasmic phospholipase A2 and PPAR-γ pathway.

Abstract

Psoriasis is a skin disease with autoimmune tendency, and taxifolin is an effective flavonoid with anti-inflammatory activity. It has been reported that taxifolin alleviates psoriatic dermatitis, but the detailed regulatory mechanism of keratinocyte proliferation is unclear. In this study, we revealed the mechanism of taxifolin on imiquimod-induced inflammatory infiltration and keratinocyte over-proliferation. Our results show that taxifolin prevented proliferation cycle of keratinocyte in a concentration-dependent manner. Over-proliferation and abnormal apoptosis of epidermal cells were obvious in the mouse model of psoriasis induced by imiquimod. Taxifolin treatment improved erythema and scales of psoriatic lesions in mice, and reduced the proportion of CD3 + cells, especially γδT cells, in lesions and thymus. Therefore, taxifolin decreased the expression level of IL-17A-dominated inflammatory cytokines. Proteomic analysis showed that 30 up-regulated proteins and 23 down-regulated proteins were compared with the lesions before and after the treatment with taxifolin. Among them, cytoplasmic phospholipase A2 (cPLA2), the key enzyme of the pro-inflammatory mediator, was the most significantly down-regulated protein. And enriched KEGG pathway shown that PPAR-γ pathway was most involved. Taxifolin significantly reduced p-cPLA2 and increased PPAR-γ protein level in keratinocytes and lesions induced by IL-17 and imiquimod respectively. Meanwhile, phosphorylation of ERK and P-38 were also inhibited. These results suggest that taxifolin prevented imiquimode-induced excessive immune activation and keratinocyte proliferation by decreasing p-cPLA2 and regulating the PPAR-γ pathway. Our study provides new insights into the cellular regulatory mechanisms of taxifolin in psoriasis.

• Authors: Tingting Di, Chunyan Zhai, Jingxia Zhao, Yan Wang, Zhaoxia Chen, Ping Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 99 Pg. 107900 (Oct 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34233233 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• PPAR gamma
• Quercetin
• taxifolin
• Mitogen-Activated Protein Kinases
• Phospholipases A2
• Imiquimod

Topics

• Animals
• Cell Line
• Cell Proliferation (drug effects)
• Cytoplasm (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Humans
• Imiquimod
• Keratinocytes (drug effects, metabolism)
• Male
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (metabolism)
• PPAR gamma (metabolism)
• Phospholipases A2 (metabolism)
• Phosphorylation (drug effects)
• Proteomics
• Psoriasis (chemically induced, drug therapy, metabolism)
• Quercetin (analogs & derivatives, pharmacology, therapeutic use)
• Signal Transduction (drug effects)