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

Mohsen Rokni; Elham Farhadi; Hoda Kavosi; Maryam Akhtari; Elham Madreseh; Samaneh Enayati; Mina  Sadeghi Shaker; Shayan Mostafaei; Farhad Gharibdoost; Mahdi Mahmoudi; Mohammad Vodjgani

doi:10.18502/ijaai.v23i2.15325

Mohsen Rokni Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Maryam Akhtari Tobacco Prevention and Control Research Center (TPCRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Elham Madreseh Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Samaneh Enayati Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mina Sadeghi Shaker Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Shayan Mostafaei Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Farhad Gharibdoost Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Vodjgani Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v23i2.15325

Keywords: Dexamethasone; Fibrosis; Inflammation; Interferon-gamma; IRF1; Systemic sclerosis

Abstract

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 (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-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 IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ 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.

IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate 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 IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA.

Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.