Decreased induction of IL-1β in fibroblast-like synoviocytes: A possible regulatory mechanism maintaining joint homeostasis

Abstract

The response of fibroblast-like synoviocytes (FLS) to inflammatory stimuli was compared to their, respectively, derived dermal fibroblasts (DF) to determine whether regulatory controls exist within FLS to insure normal joint homeostasis. We further analyzed whether the loss of the normal regulatory controls present within the FLS could predispose to the development of non-rheumatic joint disease (non-RA). Primary fibroblast cell lines were generated from synovial and skin tissue from ten rheumatoid arthritis (RA) and ten non-RA patients. Cell lines were pulse labeled with [ 35S]-methionine and stimulated with TNFα or IL-1β. Protein synthesis of IL-1β, IL-6 and IL-8 was quantitated following immunoprecipitation. Gene expression was determined by Northern blot analysis. We noted, IL-1β was minimally detected in FLS under nonstimulated conditions. In response to stimulation with IL-1β or TNFα, production of IL-1β was found to be 3.5 and 5-fold lower in FLS, respectively, when compared to DF from the same individual. In contrast, the production of IL-6 and IL-8 in FLS upon stimulation was 3-fold and 1.6-fold higher, respectively, than in DF. Furthermore, induced IL-1β production in FLS, normalized relative to their, respectively, stimulated DF, was 2.5 times higher in non-RA versus RA-derived cells ( p = 0.032), an effect noted even after several passages of growth. Our data suggest that inductive expression of IL-1β in FLS is under specific inhibitory control. Increased production of IL-1β in FLS of susceptible individuals may lead to a higher risk of developing severe joint damage even in the absence of systemic inflammation.