Interferon-γ Induces Interleukin-6 Production and Alpha-smooth Muscle Actin Expression in Systemic Sclerosis Fibroblasts

Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-gamma) and dexamethasone (DEX) on the IRF1, extracellular signal -regulated kinase 1/2 (ERK1/2), and the expression of alpha -smooth muscle actin ( alpha- SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFN gamma and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFN gamma and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFN gamma could up -regulate some of the inflammation -related genes (Interleukin-6; IL6 ) and downregulate some of the fibrosis -related genes ( COL1A1 ) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFN gamma can induce fibroblast differentiation to the myofibroblast that expresses alpha-SMA. Concerning the inhibitory effect of IFN gamma on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFN gamma may play a dual role in SSc.