Resveratrol Ameliorates Imiquimod-Induced Psoriasis-Like Mouse Model via Reducing Macrophage Infiltration and Inhibiting Glycolysis

Abstract

Purpose

Resveratrol (Res) is a natural polyphenol with anti-inflammatory and immunomodulatory effects. Alterations in metabolic pathways have been studied in psoriasis. This study is aimed to further explore the potential molecular mechanism of psoriasis improvement by Res.

Patients and Methods

Imiquimod (IMQ)-induced psoriasis-like mouse model was established to observe the effects of Res. NanoString nCounter Metabolic Pathways Panel was used to analyze the changed mRNA and qRT-PCR was used for validation. Flow cytometry was used to analyze immune cell subsets in skin lesions. In vitro, we observed the effects of Res on R848-stimulated macrophages glycolysis and inflammation.

Results

Res reduced the proliferation of keratinocytes and the secretion of inflammatory cytokines in IMQ-induced psoriasis-like mouse model. Psoriasis model skin lesions were in a state of hypoxia, with upregulated glycolysis and downregulated AMPK activity. Res inhibited the levels of hypoxia-related genes (hif1α, hif3α) and glycolysis-related genes (hk1, ldha), meanwhile increased the levels of AMPK genes (prkaa1, prkaa2). Flow cytometry analysis revealed that Res decreased the infiltration of macrophages in psoriasis-like lesions. In addition, Res decreased the secretion of macrophage-associated pro-inflammatory cytokines (IL-23, TNF-α, IL-1β). In vitro, Res diminished the secretion of IL-23, TNF-α, IL-1β, and lactate by R848-stimulated macrophages and activated AMPK.

Conclusion

This study suggested that Res diminished psoriasis symptoms by inhibiting macrophages infiltration and inhibiting glycolysis, which providing novel insights into the underlying mechanisms of therapeutic action of Res in the treatment of psoriasis.

Keywords:

• resveratrol
• psoriasis
• macrophage
• AMPK
• glycolysis

Abbreviations

AMPK, AMP-activated protein kinase; Arg1; Arginase-1; Cpt1a, carnitine palmitoyltransferase 1A; FAO, fatty acid oxidation; HK, hexokinase; IL17A, Interleukin-17A; IMQ, imiquimod; LDHA, lactate dehydrogenase A; OXPHOS, oxidative phosphorylation; PDEs, Phosphodiesterases; Res, resveratrol; TCA, tricarboxylic acid; TLR, Toll-like receptor; ROS, reactive oxygen species.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 82074180, 82074435) and supported by Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis for technical assistance.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.