Abstract
Interleukin-33 (IL-33), a member of the IL-1 superfamily, has been shown to play a critical role in many diseases through regulating the immune cell responses, including myeloid-derived suppressor cells (MDSCs). Our previous study demonstrated that IL-33 might play a protective role in kidney injury in gout patients by regulating the lipid metabolism. However, the role of IL-33in the development of MSU-induced inflammation remains elusive. In this study, an increased IL-33 expression was observed in gout patients, which was positively correlated with inflammatory marker CRP. To explore the effects and mechanisms of the increased IL-33 expression in the gout patients, the anti-ST2 antibody and exogenous recombinant IL-33 were used in MSU-induced peritonitis animal model that mimics human gout. Compared with control group, mice with exogenous recombinant IL-33 significantly ameliorated the inflammatory cells infiltration, while blockage of IL-33 signaling by anti-ST2 had no effect on the development of MSU-induced peritonitis. Furthermore, the crucial inflammatory cytokine IL-1β was markedly decreased in IL-33-treated mice. Besides that, a large number of anti-inflammatory MDSCs with CD11b+Gr1intF4/80+ phenotype was observed in the IL-33-treated mice, and adoptive transfer of IL-33-induced MDSCs (CD11b+Gr1intF4/80+) markedly inhibited the IL-1β production in MSU-induced peritonitis. In conclusion, our data provide clear evidences that the increased expression of IL-33 in the gout patients might be due to a cause of self-negative regulation, which inhibits the development of MSU-induced inflammation through expanding MDSCs. Thus, IL-33 might serve as a promising therapeutic target for gout.
Highlights
Gout is the most common inflammatory arthritis caused by inflammatory responses to the deposition of monosodium urate (MSU) crystals
We speculate that an increased expression of IL-33 in the gout patients might be due to a cause of self-negative regulation, while the increased amount of IL-33 expression was inadequate to induce a potent protective effect to reduce the development of gout
We found an increased level of IL-33 in gout patients, which was positively correlated with inflammatory marker C-reactive protein (CRP)
Summary
Gout is the most common inflammatory arthritis caused by inflammatory responses to the deposition of monosodium urate (MSU) crystals. The uric acid levels exceed the physiological saturation concentration, which will lead to monosodium urate crystal (MSU) formation [1]. MSU crystals trigger an intense inflammatory response by activating the resident. IL-33 Inhibits MSU-Induced Inflammation tissue macrophages and promoting the recruitment of neutrophils to the joint [2]. IL-1β is the most important proinflammatory regulatory cytokine from activated macrophage by MSU stimulation in the onset of acute gout [3]. During the development of MSU-induced inflammation, mature IL-1β production by macrophages induces activation of IL-l signaling pathways and medullary differentiation factor (MyD88)-dependent NFκB pathway, resulting in a large number of chemokines and pro-inflammatory factors being produced, and inflammatory immune cells infiltration [4]. The mechanism of inflammation self-resolution is still elusive [5, 6]
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