TRANSFORMING-GROWTH-FACTOR BETA-1 AND INTERLEUKIN-4 INDUCED ALPHA-SMOOTH MUSCLE ACTIN EXPRESSION AND MYOFIBROBLAST-LIKE DIFFERENTIATION IN HUMAN SYNOVIAL FIBROBLASTS IN-VITRO - MODULATION BY BASIC FIBROBLAST GROWTH-FACTOR

Objective-To discover if a smooth muscle actin expression and myofibro blastic differentiation are induced in synovial fibroblasts by cytokin es found in the inflamed RA joint. Methods-Immunofluorescent microscop y and western blotting were used to examine different cultures of huma n synovial fibroblasts for expression of a actin in the presence of th e cytokines transforming growth factor beta (TGF beta 1), interleukin 1 alpha (IL1 alpha), IL4, IL6, tumour necrosis factor alpha (TNF alpha ), and basic fibroblast growth factor (FGF). Results-A small but signi ficant population of cells (14.4 +/- 12.9%) expressed alpha actin unde r standard culture conditions. Upon treatment with TGF beta 1 there wa s a pronounced increase in the number of cells expressing alpha actin (68.1 +/- 5.49%), accompanied by a change in morphology to a myofibrob last-like phenotype. Other cytokines found within the inflamed joint s uch as IL1, TNF alpha, IL6, and basic FGF failed to induce alpha actin expression. However, IL4, which is normally absent or only present at low concentrations in the RA joint had a similar effect to TGF beta 1 . It was also found that basic FGF inhibited the induction of alpha ac tin expression by TGF beta 1 and IL4. Conclusion-In the presence of TG F beta 1 or IL4, fibroblasts derived from synovial tissue or synovial fluid are induced to differentiate into myofibroblast-like cells conta ining the alpha smooth muscle form of actin. This differentiation is i nhibited by basic FGF. It is suggested that the balance between these particular cytokines may be important in the modulation of fibroblast behaviour, which could have significant effects on joint repair mechan isms and the generation of fibrous tissue within the rheumatoid joint.