Ultraviolet B inhibits IL-17A/TNF-α-stimulated activation of human dermal fibroblasts by decreasing the expression of IL-17RA and IL-17RC on fibroblasts

Abstract

Background: Psoriasis is a chronic immune-mediated inflammatory disease, and a mixed Th1/Th17 cytokine environment plays a critical role in the pathogenesis of psoriasis. Dermal fibroblasts secrete certain cytokines such as IL-6, IL-8, and CXCL-1, contributing to the hyperproliferative state of the epidermis in psoriatic skin. Ultraviolet B (UVB) phototherapy is one of the most commonly used treatments in psoriasis but the influence of UVB on human dermal fibroblasts (HDFs) in psoriasis treatment is not completely understood. Objectives: We conducted this study to mimic a psoriatic microenvironment in order to investigate and illustrate the combined effects of UVB, IL-17A, and TNF-α on HDFs. Methods: The cultured HDFs were obtained from foreskin samples and divided into four groups, as follows: control; IL-17A/TNF-α; UVB; and IL-17A/TNF-α + UVB. Cultured HDFs were irradiated with 30 mJ/cm2 UVB followed by addition of IL-17A/TNF-α and incubated for 24 h. We used real-time quantitative PCR, Western blot, ELISA analysis, and flow cytometry to examine gene and protein expression of related pro-inflammatory cytokines and chemokines and receptors. Results: HDFs produced significant IL-6, IL-8, and CXCL-1 in response to IL-17A/TNF-α stimulation and UVB irradiation but UVB irradiation inhibited IL-17A/TNF-α-induced IL-6, IL-8, and CXCL-1 expression and downregulated the expression of IL-17RA and IL-17RC at both gene and protein levels. Additionally, UVB irradiation induced significant TGF-β1 protein secretion and expression of Smad3 mRNA and protein by HDFs. TGF-β1 significantly induced the expression of Smad3 mRNA and downregulated the IL-17RA and IL-17RC expression on HDFs. Conclusion: UVB irradiation inhibits IL-17A/TNF-α-induced IL-6, IL-8, and CXCL-1 production in HDFs by decreasing the expression of IL-17RA and IL-17RC on fibroblasts through TGF-β1/Smad3 signaling pathway, which reveals a new mechanism of the therapeutic action of UVB on psoriasis.