Stimulation of the hyaluronic acid levels of human synovial fibroblasts by recombinant human tumor necrosis factor α, tumor necrosis factor β (lymphotoxin), interleukin‐1α, and interleukin‐1β

Abstract

Monocyte/macrophage polypeptides (monokines) alter the properties of synovial cells. This interaction could explain some of the properties of the inflamed synovium in rheumatic disease. Only recently has it been possible to test the action of purified monokines on the target synovial cells. We report here that recombinant human tumor necrosis factor a, tumor necrosis factor p (Lymphotoxin), interleukin-lcu, and interleukinlp stimulate the hyaluronic acid (HA) levels of human synovial fibroblast-like cells. The effect of monokines was generally inhibited by indomethacin, suggesting the involvement of an endogenous cyclooxygenase product in the stimulation, and by the glucocorticoid, dexamethasone. In contrast, all-trans-retinoic acid stimulated synovial cell plasminogen activator activity but did not increase the HA levels. These findings could help to explain the raised HA levels found in the joint fluids and in the circulation of patients with rheumatic disease.It is widely believed that the damage occurring in the joints of patients with rheumatoid arthritis (RA) and related diseases depends largely on pathologic changes in the synovial tissue. These changes probably arise from an immune response to an unidentified antigen, a consequence of which could be the modu-

Synergistic, additive, and antagonistic effects of interleukin‐1β, tumor necrosis factor α, and γ‐interferon on prostaglandin e, hyaluronic acid, and collagenase production by cultured synovial fibroblasts

“…Other studies have shown IL-1 to be more potent than TNFa in stimulating PGE production in cultures of human synovial cells (17,25,31), dermal fibroblasts (13), lung fibroblasts (21), and mesangial cells (32), collagenase production in cultures of dermal fibroblasts (13,33), and HA or glycosaminoglycan production by synovial cells (16) and dermal fibroblasts (33). In another study with synovial cells, TNFa was reported to be slightly more effective than IL-1 in stimulating PGE, and collagenase release (13); however, this may have been due to the use of murine cytokines, whose effects on human synovial cultures differ from those of human cytokines (31).…”

Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis

“…Elevated concentrations of HA in the serum of RA patients appear to be related to acceler- ated production of HA in inflamed joints, and the resultant increase in the amount of degradation products appearing in the serum (17)(18)(19)(20). Monokines, especially tumor necrosis factor CY and interleukin-1 a, which are detected in increased quantities in the joints of RA patients (21,22), stimulate HA production by synovial fibroblast-like cells (23). Serum levels of HA may thus better reflect local inflammatory processes than do the ESR and CRP, which are partially dependent on extraarticular mechanisms.…”

Regulation of hyaluronan synthase-2 expression in human intestinal mesenchymal cells: mechanisms of interleukin-1β-mediated induction

“…IFN-␥, IL-1, and transforming growth factor-␤ 1 have been shown to stimulate hyaluronan production of orbital fibroblasts (60). IL-1␣, IL-1␤, and TNF-␣ also stimulate the expression of hyaluronan by synovial fibroblasts (8). We and others have shown that IL-␤ and TNF-␣ stimulate the expression of hyaluronan in human dermal fibroblasts (34,45,46).…”