title: 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.
  
  
  OBJECTIVE
  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/cm2UVB 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: YingYing
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: JiaLi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
authors.forename: ZhiQiang
authors.initials: Z
authors.lastname: Yin
keywords: IL-17; TGF-β; TNF-α; fibroblast; psoriasis; ultraviolet