IL-1βand TNFαPromote Monocyte Viability through the Induction of GM-CSF Expression by Rheumatoid Arthritis Synovial Fibroblasts

Abstract

Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone (P < 0.001). This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF (P < 0.001). Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization.

Dectin-2–induced CCL2 production in tissue-resident macrophages ignites cardiac arteritis

“…Because Dectin-2 expression is restricted to myeloid cells (44), it is likely that cardiac fibroblasts are not directly responding to CAWS, but instead are stimulated by cytokines, such as IL-1β, to produce GM-CSF. As IL-1β is known to be a classical inducer of GM-CSF in physiological and pathological conditions (45), and IL-1β promotes GM-CSF production from fibroblasts (46), IL-1β is a potential upstream stimulator of fibroblast-derived GM-CSF production. However, Stock et al have argued that IL-1 signaling is not essential for the development of cardiac vasculitis (25).…”

<b>Interleukin-1β and Tumor Necrosis Factor-α Synergistically Induce Expression of Colony Stimulating Factors in Synovial Fibroblasts from the Human Temporomandibular Joint</b>

“…Additionally, CSFs are also reported to have many proinflammatory functions and function as key factors in inflammatory conditions of joints such as RA (17)(18)(19). We also investigated the effects of stimulation of proinflammatory cytokines such as IL-1 and/or TNF-on the gene expression and production of CSFs in synovial fibroblasts from TMJ patients.…”

Immunomodulatory activity of essential oil from Tetrania riparia (Hochstetter) Codd in murine macrophages

“…High levels of GM‐CSF have been associated with the exacerbation of arthritis, autoimmune encephalomyelitis, atherosclerosis, Xnephritis, lung inflammation, and cancer. GM‐CSF is involved in disease mechanisms and could be a viable target for arthritis and cancer therapy . Thus, TrEO may also contribute to the treatment of infectious diseases and other conditions in which GM‐CSF production is excessively high.…”

“…GM-CSF is involved in disease mechanisms and could be a viable target for arthritis and cancer therapy. [49,50] Thus, TrEO may also contribute to the treatment of infectious diseases and other conditions in which GM-CSF production is excessively high.…”