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Research Article
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
DOI: 10.1002/art.22010
Copyright © 2006 by the American College of Rheumatology
1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e "Arthritis & Rheumatism")
Additional Information
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
Publication History
- Issue published online: 25 JUL 2006
- Article first published online: 25 JUL 2006
- Manuscript Accepted: 21 APR 2006
- Manuscript Received: 16 JUN 2005
Funded by
- NIH. Grant Number: R01-AR-19616 (principal investigator SAJ)
- Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
- Abstract
- Article
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- Cited By
Abstract
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.