Inhibition of lymphocyte adhesion to cytokine-activated synovial fibroblasts by glucocorticoids involves the attenuation of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 gene expression.
OBJECTIVE
The aim of this study was to evaluate the ability of glucocorticoids to inhibit lymphocyte adhesion to human synovial fibroblasts.


METHODS
Adhesion of lymphocytes to cultured synovial fibroblasts was measured by counting the number of cells bound to fibroblasts. Surface expression of intercellular adhesion molecule 1 (ICAM-1) was measured by enzyme-linked immunosorbent assay, while vascular cell adhesion molecule 1 (VCAM-1) surface expression was measured by flow cytometry. ICAM-1 and VCAM-1 messenger RNA (mRNA) levels were assessed by Northern blot analysis.


RESULTS
Stimulation of synovial fibroblasts by the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, and interferon-gamma resulted in a dose-dependent increase in lymphocyte adhesion to synovial fibroblasts. This response was inhibited by preincubation of the cells with the synthetic glucocorticoid dexamethasone. Since lymphocyte adhesion to synovial fibroblasts is known to be mediated by VCAM-1 and ICAM-1, we examined the modulation of VCAM-1 and ICAM-1 expression in these cells. All 3 cytokines stimulated VCAM-1 and ICAM-1 surface and mRNA expression. Dexamethasone inhibited both VCAM-1 and ICAM-1 surface and mRNA expression in a dose-dependent manner, which correlated with the inhibition of lymphocyte adhesion.


CONCLUSIONS
Taken together, these results suggest that glucocorticoids may reduce inflammatory responses at extravascular sites by inhibiting the expression of these adhesion molecules, thereby reducing the adhesion of lymphocytes to connective tissue cells.
Tessier
P A
PA
Centre de Recherche du CHUL, Université Laval, Ste-Foy, Quebec, Canada.
Cattaruzzi
P
P
McColl
S R
SR
D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008214:Lymphocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D016207:Cytokines; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone