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 (≤ 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in a dose-dependent fashion. Systemic sclerosis dermal fibroblasts appeared to be hyperresponsive to IL-1β, TNF-α, and IFN-γ. 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.

Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients

“…Koch et al reported that TNFα expression was increased on SSc stratum granulosum, especially in early SSc and suggested that TNFα may play a part in the early inflammatory stage of SSc 16. Systemic sclerosis dermal fibroblasts were reported to be hyperresponsive to TNFα and expression of ICAM-1 was increased to a greater degree in response to TNFα stimulation 17. Based on these and other reports9 10 we suggest that TNFα might play a part in the pathogenesis of scleroderma.…”

Analysis of TNF Polymorphisms in Turkish Systemic Sclerosis Patients with Interstitial Lung Involvement

“…Systemic sclerosis dermal fibroblasts were reported to be hyperresponsive to TNF-a, and expression of intercellular adhesion molecule 1 (ICAM-1) was increased to a greater degree in response to TNF-a stimulation (Cho et al 1994). Based on these and other reports (Moffatt and Cookson 1997;Fernandez-Arquero et al 1999), we suggest that TNF-a might play a role in the pathogenesis of scleroderma.…”

Cytokine profiles in localized scleroderma and relationship to clinical features

“…Studies conducted by Thornton et al have found lower concentrations of TNF-α to stimulate fibroblast synthesis and higher levels to be inhibitory [15]. SSc analyses conducted in vitro have implicated TNF-α as a potential contributor to fibrosis, demonstrating SSc dermal fibroblasts to be hyperresponsive to TNF-α [16]. In vivo studies have illustrated elevated serum levels of TNF-α to be significantly correlated with the presence of pulmonary fibrosis [17].…”