Regulation of the expression of intercellular adhesion molecule 1 in cultured human endothelial cells derived from rheumatoid synovium

Abstract

Objective. To examine the regulation of intercellular adhesion molecule 1 (ICAM-1) in human synovial microvascular endothelial cells (HSE) and human umbilical vein endothelial cells (HUVE) upon exposure to a variety of agents.Methods. Cultured endothelial cells were treated with various cytokines alone and in combination. The expression of ICAM-1 was evaluated at several levels, including an investigation of messenger RNA (mRNA) and surface protein expression.Results. Treatment of HSE with interleukin-la (IL-la) or tumor necrosis factor a (TNFa) resulted in minimal increases in ICAM-1 expression, in contrast to findings with HUVE. Incubation of HUVE or HSE with IL-1 or TNF in combination with interferon-y (IFNy) greatly potentiated the increase in ICAM-1 surface expression. The synergistic effect of IFNy and TNF was confirmed by several methods, including a cell-based enzyme-linked immunosorbent assay, tluorescenceactivated cell sorting, immunofluorescence staining, and determination of mRNA levels. IFN y also augmented the actions of several other agonists on HSE, i.e., IL-4, lipopolysaccharide, and TNFPllymphotoxin. an identical manner. Unexpectedly, IFNy alone was a potent stimulus for HSE ICAM-1 mRNA synthesis, but was relatively ineffective in HUVE.Conclusion. These studies indicate that IFNy plays a critical synergistic role in the regulation of ICAM-1 expression in human synovial endothelial cells.

Regulation of adhesion molecule expression by human synovial microvascular endothelial cells in vitro

“…In this study, we demonstrated that SMEC, as well as DEC, consistently expressed high levels of ICAM-1 under basal culture conditions. Our findings differ from those of Gerritsen et a1 (9), who showed no difference between SMEC and HUVE in their basal ICAM-1 expression. Those authors also showed that treatment of SMEC with TNFa for 24 hours resulted in minimal increases in ICAM-1 expression compared with HUVE.…”

“…Therefore, to study synovial endothelial cell properties in vitro, it is preferable to isolate purified synovial microvascular endothelial cells (SMEC) from the target tissue. However, the number of reports of in vitro studies with these cells has been limited, due to the difficulties in isolation and culture (8)(9)(10). We have successfully used Ulex-coated Dynabeads, a method originally developed in our laboratory (1 l), to isolate SMEC from RA, osteoarthritic (OA), and normal synovia, as well as microvascular endothelial cells from neonatal foreskin (FSE) and from deciduum.…”

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

“…The inflammatory ST state was determined by histological analysis and the results were in accordance with the observed overexpression of ICAM-1 and VCAM-1, where increased RA and OA ST adhesiveness may promote interactions with infiltrating inflammatory cells, contributing to the accumulation of leucocytes in the joint tissue [32,37,38,54]. In fact, it is well known that ICAM-1 and VCAM-1 are overexpressed in synovial membrane after stimulation with proinflammatory cytokines such as IL-1␤ and/or TNF-␣, or IL-6 [31,35,[55][56][57]. The data obtained in this study have shown that ICAM-1 and VCAM-1 expression was greater in RA synovium than in OA ST.…”

Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E‐selectin and intercellular adhesion molecule 1 expression

“…7 and 8). ICAM-1 is an important mediator of leukocyte adhesion in RA and is widely expressed in the rheumatoid synovium (vascular endothelium, lining and infiltrating macrophages) at higher levels than in normal noninflamed synovium (15,17,(22)(23)(24)(25)(26)(27). Antibodies to ICAM-1 partially inhibit leukocyte binding to synovial fibroblasts in vitro (22), and when used to treat RA, they cause a modest improvement in symptoms associated with peripheral blood neutrophilia (48).…”