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

Abstract

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 β-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-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways induced by C. acnes. FGF21 also significantly reduced the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Taken together, these findings indicate that FGF21 suppresses C. acnes-induced inflammation and might be used clinically in the management and treatment of acne.

Effects of 15% Azelaic Acid Gel in the Management of Post-Inflammatory Erythema and Post-Inflammatory Hyperpigmentation in Acne Vulgaris

“…Additionally, inflammation diminishes sulfhydryl groups in the skin, hampering tyrosinase activity and augmenting melanin production. Cutibacterium acnes has been implicated in elevating messenger RNA (mRNA) expression of TNF-alpha, secretion levels of IL-6 and IL-8, mRNA levels of tyrosinase, and dopachrome tautomerase, consequently activating melanocytes and increasing melanin output [15]. A comparative analysis of soluble proteins in pathological sections of acne-induced PIE and PIH revealed elevated levels of dermal remodeling proteases and inhibitors in PIE lesions, indicative of dermal remodeling during excision [16].…”

Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes

“…Thus, here we discuss the role of each of these cytokines in the modulation of skin inflammation and healing. In fact, IL-1β was reported as a potent pro-inflammatory cytokine that is synthesized and released by keratinocytes upon activation of Staphylococcus aureus [ 15 ] and by fibroblast upon activation of Cutibacterium acnes [ 17 ], and its increased levels are related to cell death and damage. The present study showed for the first time that hydrolyzed collagen reduced IL-1β secretion by skin fibroblasts and keratinocytes.…”

The updates and implications of cutaneous microbiota in acne

“…Notably, TNFAIP3 tempers the inflammation triggered by C. acnes in keratinocytes [ 91 ]. Recent evidence also implicates fibroblast growth factor 21 (FGF21) in exerting anti-inflammatory effects on the epidermal layer [ 92 ]. In keratinocytes, FGF21 acts to mitigate the activation of TLR2, NF-κB, and MAPK signaling prompted by C. acnes [ 92 ].…”

“…Recent evidence also implicates fibroblast growth factor 21 (FGF21) in exerting anti-inflammatory effects on the epidermal layer [ 92 ]. In keratinocytes, FGF21 acts to mitigate the activation of TLR2, NF-κB, and MAPK signaling prompted by C. acnes [ 92 ]. Moreover, FGF21 curbs the inflammation driven by C. acnes [ 92 ], suggesting its regulatory role in acne pathogenesis.…”

“…In keratinocytes, FGF21 acts to mitigate the activation of TLR2, NF-κB, and MAPK signaling prompted by C. acnes [ 92 ]. Moreover, FGF21 curbs the inflammation driven by C. acnes [ 92 ], suggesting its regulatory role in acne pathogenesis.…”