Neuroendocrine mediators regulate production of B cell activating factor of the tumor necrosis factor family (BAFF) in human synovial fibroblasts

Abstract

B cell activating factor of the tumor necrosis factor family (abbreviated BAFF) is a cytokine important for the stimulation and survival of autoreactive B cells and, therefore, might play a role in several autoimmune disease, e.g. autoimmune arthritis. In psoriasis arthritis (PsA), BAFF correlates with disease activity and testosterone, but only in male patients, suggesting a role for sex hormones in the regulation of BAFF. Thus, we wanted to determine whether BAFF production is regulated by neuroendocrine mediators in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts. First, fibroblasts isolated from synovial tissue of RA (n = 10) and OA (n = 10) patients were cultured in the presence or absence of interferon (IFN)-γ, IL-1, lipopolysaccharide (LPS), tumor necrosis factor (TNF) and cortisol in different combinations for 24, 48, and 72 h to determine the optimal stimulation strategy for induction of BAFF production (measured by ELISA in supernatants). IFN-γ in a concentration-dependent manner induced BAFF in RA and OA fibroblasts. Interestingly, we were able to induce significantly more BAFF in synovial fibroblasts from OA patients as compared to RA patients. Additionally, IFN-γ induced BAFF production in fibroblasts (OA n = 10, RA n = 10) was decreased by α-adrenergic and increased by β-adrenergic mechanisms. Furthermore, estradiol inhibited and dihydrotestosterone increased IFN-γ production. Taken together, BAFF production in synovial fibroblasts is modulated by sex hormones and adrenergic stimuli. Therefore, the known influence of neuroendocrine mechanisms in the context of arthritis might be in part mediated by regulating BAFF production from synovial fibroblasts via regulation of IFN-γ.