The antidiabetic agent metformin inhibits IL-23 production in murine bone-marrow-derived dendritic cells

Tomoyo Matsuda-Taniguchi, Masaki Takemura, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Ayako Takai-Yumine, Masutaka Furue, Gaku Tsuji

Research output: Contribution to journalArticlepeer-review

Abstract

Psoriasis is a chronic inflammatory skin disease, and its immune mechanism has been profoundly elucidated. Biologics targeting interleukin (IL)-23 have prevented the development of psoriasis. As major sources of IL-23, dendritic cells (DCs) play a pivotal role in psoriasis; however, the regulatory mechanism of IL-23 in DCs remains unclear. IL-36γ was reported to reflect the disease activity of psoriasis. Therefore, we hypothesized that IL-36γ may affect IL-23 production in DCs. To reveal the mechanism by which IL-36γ controls IL-23 production in DCs, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-36γ. IL-36γ stimulation upregulated the mRNA and protein expression of Nfkbiz in BMDCs. Nfkbiz knockdown using siRNA transfection partially inhibited the upregulation of IL-23 mRNA expression induced by IL-36γ stimulation. Since NF-κB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-κB signaling, we examined the effect of metformin treatment on IL-36γ-induced IL-23 production. Metformin treatment impaired the phosphorylation of NF-κB induced by IL-36γ stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs. These data provided evidence that metformin treatment can inhibit IL-36γ-mediated IL-23 production in BMDCs, which might contribute to the prevention of psoriasis.

Original languageEnglish
Article number5610
JournalJournal of Clinical Medicine
Volume10
Issue number23
DOIs
Publication statusPublished - Dec 1 2021

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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