title: A possible contribution of visfatin to the resolution of skin sclerosis in patients with diffuse cutaneous systemic sclerosis via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response.
abstract: OBJECTIVE
  Visfatin is a member of the adipocytokines with pro-fibrotic, pro-inflammatory and immunomodulating properties potentially implicated in the pathogenesis of certain fibrotic and inflammatory autoimmune diseases. In this study, we investigated THE CLINICAL SIGNIFICANCE OF SERUM VISFATIN LEVELS AND ITS CONTRIBUTION TO THE DEVELOPMENTAL PROCESS IN SSC.
  
  
  METHODS
  Serum visfatin levels were determined by a specific ELISA in 57 SSc patients and 19 healthy controls. The mRNA levels of target genes were determined in normal and SSc fibroblasts by real-time RT-PCR. The levels of IL-12p70 produced by THP-1 cells were measured by a specific ELISA.
  
  
  RESULTS
  Serum visfatin levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc and healthy controls. The only finding in a series of analyses regarding the correlation of serum visfatin levels with clinical symptoms and laboratory data was the significantly longer disease duration in dcSSc with elevated serum visfatin levels than in those with normal levels. Consistently, serum visfatin levels were significantly elevated in late-stage dcSSc (disease duration >6 years), but not in early and mid-stage dcSSc compared with healthy controls. In in vitro experiments, visfatin reversed the pro-fibrotic phenotype of SSc dermal fibroblasts and induced the expression of IL-12p70 in THP-1 cells treated with IFN-γ plus lipopolysaccharide.
  
  
  CONCLUSIONS
  Visfatin may contribute to the resolution of skin sclerosis in late-stage dcSSc via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response.
authors: Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Yuri
authors: Y
authors: Masui
authors: Yoshihide
authors: Y
authors: Asano
authors: Sayaka
authors: S
authors: Shibata
authors: Shinji
authors: S
authors: Noda
authors: Kaname
authors: K
authors: Akamata
authors: Naohiko
authors: N
authors: Aozasa
authors: Takashi
authors: T
authors: Taniguchi
authors: Takehiro
authors: T
authors: Takahashi
authors: Yohei
authors: Y
authors: Ichimura
authors: Tetsuo
authors: T
authors: Toyama
authors: Hayakazu
authors: H
authors: Sumida
authors: Koichi
authors: K
authors: Yanaba
authors: Yayoi
authors: Y
authors: Tada
authors: Makoto
authors: M
authors: Sugaya
authors: Shinichi
authors: S
authors: Sato
authors: Takafumi
authors: T
authors: Kadono
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D045743:Scleroderma, Diffuse / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D012333:RNA, Messenger; D018664:Interleukin-12; D054409:Nicotinamide Phosphoribosyltransferase
keywords: collagen; interleukin-12; matrix metalloproteinase 1; systemic sclerosis; visfatin