Up-regulation of class II major histocompatibility complex and intercellular adhesion molecule 1 expression on scleroderma fibroblasts and endothelial cells by interferon-gamma and tumor necrosis factor alpha in the early disease stage.

Abstract

To investigate the expression patterns of interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), both of which are potent inducers of class II major histocompatibility complex (MHC) and intercellular adhesion molecule 1 (ICAM-1) expression, and their codistribution with HLA-DR and ICAM-1 in skin lesions, cultured fibroblasts, and peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc) patients in different stages of disease. Investigations were carried out using immunohistochemistry studies, reverse transcriptase-polymerase chain reaction, dot-blot hybridization, and cytometric analysis. Serum levels of TNF alpha were determined by enzyme-linked immunosorbent assay. In the early inflammatory stage of SSc, class II MHC and ICAM-1 expression could be detected on most endothelial cells and on fibroblasts located especially in perivascular areas surrounded by infiltrating lymphocytes, which belong to the T helper 1 phenotype expressing IFN gamma and TNF alpha. In this early disease stage, an enhanced expression of TNF alpha on cultured dermal fibroblasts and PBMC, as well as elevated serum titers of soluble TNF alpha, could be found. These data suggest that class II MHC antigens and ICAM-1 on fibroblasts and endothelial cells are induced by IFN gamma and TNF alpha in an early stage of SSc after the influx of mononuclear-cells, and may be important in the putative autoimmune response and in the perpetuation of fibrotic processes in SSc.