In vitro Cytokine Modulation of Intercellular Adhesion Molecule-1 Expression on Systemic Sclerosis Dermal Fibroblasts

Abstract

Our objective was to study the regulation of intercellular adhesion molecule-1 (ICAM-1) expression by cytokines on cultured fibroblasts obtained from systemic sclerosis and normal skin. ICAM-1 expression on dermal fibroblasts obtained from diffuse systemic sclerosis patients with early disease (< or = 2 years) and normal dermal fibroblasts incubated with and without cytokines was measured by radioimmunoassay and flow cytometry. Systemic sclerosis dermal fibroblasts expressed lower basal levels of ICAM-1 than did normal dermal fibroblasts. Both the normal and systemic sclerosis dermal fibroblasts increased their cell surface expression of ICAM-1 in response to interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in a dose-dependent fashion. Systemic sclerosis dermal fibroblasts appeared to be hyperresponsive to IL-1 beta, TNF-alpha, and IFN-gamma. ICAM-1 expression in response to cytokine stimulation increased to a greater degree on systemic sclerosis compared to normal dermal fibroblasts. The enhanced ICAM-1 expression may play a role in the retention of leukocytes involved in systemic sclerosis skin lesions.