Interleukin-33 Synergistically Enhances Immune Complex-Induced Tumor Necrosis Factor Alpha and Interleukin-8 Production in Cultured Human Synovium-Derived Mast Cells

Abstract

Background: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-33 is believed to play an important role in the pathogenesis of RA. We recently reported that FcγRI is responsible for producing abundant tumor necrosis factor alpha (TNF-α) from cultured synovium-derived MCs (SyMCs) in response to aggregated immunoglobulin G (IgG). However, whether or not IL-33 affects immune complex (IC)-induced synovial MC activation remains unknown. This study sought to evaluate the effect of IL-33 on IC-induced synovial MC activation. Methods: Cultured SyMCs were generated by culturing synovial cells with stem cell factor. ST2 expression was analyzed using FACS and immunohistochemical techniques. Mediators released from the MCs were measured using EIAs or ELISAs. Results: SyMCs obtained from patients with RA or osteoarthritis (OA) expressed ST2 on their surfaces. We confirmed the expression of ST2 in MCs using immunofluorescence staining in joint tissue obtained from RA patients. IC-triggered histamine release was not enhanced by IL-33. However, IL-33 synergistically enhanced IC-induced IL-8 and TNF-α production in SyMCs. Conclusions: ICs and IL-33 may exacerbate inflammation associated with RA by abundantly producing TNF-α and IL-8 from SyMCs.

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

“…In mouse models of arthritis involving active immunization, the use of ST2 KO mice, ST2 blockade, or injection of sST2 decreased immune responses and severity of arthritis. This finding suggested a pathogenic role for IL-33, signaling through ST2L, in these experimental models (20)(21)(22). However, although arthritis is reduced in ST2 KO mice, it did not differ in IL-33 KO mice compared with wild-type mice (25,26).…”

“…IL-33 levels in serum and synovial fluid are elevated, and a strong IL-33 expression can be detected in RA synovium (19,20). IL-33 synergistically enhances immune complex-induced TNF-a and IL-8 production in cultured human synovium-derived mast cells (21). In mouse models, whereas arthritis is reduced in ST2 knockout (KO) or in anti-ST2-treated mice x Institut de Pharmacologie et de Biologie Structurale CNRS-Université de Toulouse III, F-31000 Toulouse, France; and (22)(23)(24), it does not differ in IL-33 KO mice compared with wild-type mice (25,26).…”

Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2

“…IL-1 receptorlike 1, encoded by IL1RL1, is a receptor for IL-33. IL1RL1 is induced by proinflammatory stimuli, and IL1RL1, like IL-6, is implicated in inflammation-associated disease states (26)(27)(28).…”

The Sound of a Buk (Korean Traditional Drum) Attenuates Anaphylactic Reactions by the Activation of Estrogen Receptor-β

“…Choi et al [27] reported that hesperidin reduced the expression of TNF-α by suppressing HIF-1α in mast cells. TNF-α is released from mast cells by degranulation and aggravates allergic symptoms by inducing neutrophil chemotaxis and the production of other inflammatory cytokines [28,29,30]. Our results show that Buk music down-regulated TNF-α protein levels, which suggests Buk music down-regulated TNF-α by inhibiting HIF-1 activation.…”