4.7 Article

Suppression of Cutibacterium acnes-Mediated Inflammatory Reactions by Fibroblast Growth Factor 21 in Skin

Journal

Publisher

MDPI
DOI: 10.3390/ijms23073589

Keywords

Cutibacterium acnes; fibroblast growth factor 21; skin inflammation; keratinocyte-fibroblast cross talk

Funding

  1. National Natural Science Foundation of China [82070507]
  2. Natural Science Foundation of Zhejiang Province [LY22H110002, LZ21H020002]
  3. Sciences and Technology Program of Wenzhou [Y2020177]

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The study demonstrates that FGF21 can suppress inflammation induced by C. acnes through counteracting activation of TLR2, NF-κB, and MAPK signaling pathways and reducing the expression of inflammatory cytokines.
Cutibacterium acnes (C. acnes) is a common commensal bacterium that is closely associated with the pathogenesis of acne. Fibroblast growth factor 21 (FGF21), as a favorable regulator of glucose and lipid metabolism and insulin sensitivity, was recently shown to exert anti-inflammatory effects. The role and mechanism of FGF21 in the inflammatory reactions induced by C. acnes, however, have not been determined. The present study shows that FGF21 in the dermis inhibits epidermal C. acnes-induced inflammation in a paracrine manner while it functions on the epidermal layer through a receptor complex consisting of FGF receptor 1 (FGFR1) and beta-Klotho (KLB). The effects of FGF21 in heat-killed C. acnes-induced HaCaT cells and living C. acnes-injected mouse ears were examined. In the presence of C. acnes, FGF21 largely counteracted the activation of Toll-like receptor 2 (TLR2), the downstream nuclear factor-kappa B (NF-kappa B), and mitogen-activated protein kinase (MAPK) signaling pathways induced by C. acnes. FGF21 also significantly reduced the expression of proinflammatory cytokines, including interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Taken together, these findings indicate that FGF21 suppresses C. acnes-induced inflammation and might be used clinically in the management and treatment of acne.

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