Open AccessExpression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor β
Author(s) -
Galdo Francesco Del,
Maul Gerd G.,
Jiménez Sergio A.,
Artlett Carol M.
Publication year - 2006
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.22010
Subject(s) - gene isoform , biology , messenger rna , growth factor , cytokine , pathogenesis , transforming growth factor beta , immune system , transforming growth factor , stimulation , immunology , pathology , microbiology and biotechnology , medicine , endocrinology , receptor , gene , biochemistry
Objective Allograft inflammatory factor 1 (AIF‐1), a protein initially identified in chronically rejected rat cardiac allografts, is involved in the immune response and proliferative vasculopathy that occurs during allograft rejection. Three well‐characterized isoforms of AIF‐1 result from alternative messenger RNA (mRNA) splicing. We previously identified a strong association of systemic sclerosis (SSc) with a polymorphism in AIF‐1 isoform 2. The purpose of this study was to investigate AIF‐1 expression in affected tissues from patients with SSc and to examine the regulation of its isoforms by transforming growth factor β (TGFβ). Methods AIF‐1 in the skin and lung tissues of patients with SSc was analyzed by immunochemistry. AIF‐1 isoform expression in response to TGFβ and interferon‐γ stimulation was examined by quantitative polymerase chain reaction (PCR). Results AIF‐1 protein was present in affected vessels of the lung and skin lesions of patients with SSc. Quantitative PCR showed an average of 14‐fold higher mRNA levels in affected SSc skin than in normal skin. Double‐label immunofluorescence staining demonstrated that T cells, macrophages, and endothelial cells in affected tissues expressed AIF‐1. Stimulation of peripheral blood mononuclear cells with TGFβ caused a specific and significant increase in the expression of AIF‐1 isoform 2 transcripts ( P < 0.005), which was due to stabilization of AIF‐1 isoform 2 mRNA. Conclusion These data suggest that AIF‐1 plays an important role in the pathogenesis of SSc owing to its increased expression in affected tissues and to the specific stimulation of AIF‐1 isoform 2 by TGFβ.