Expression 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
Article first published online: 25 JUL 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 8, pages 2616–2625, August 2006
How to Cite
Galdo, F. D., Maul, G. G., Jiménez, S. A. and Artlett, C. M. (2006), Expression 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. Arthritis & Rheumatism, 54: 2616–2625. doi: 10.1002/art.22010
- Issue published online: 25 JUL 2006
- Article first published online: 25 JUL 2006
- Manuscript Accepted: 21 APR 2006
- Manuscript Received: 16 JUN 2005
- NIH. Grant Number: R01-AR-19616 (principal investigator SAJ)
- Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
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).
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).
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.
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.