Macrophage migration inhibitory factor drives neutrophil accumulation by facilitating IL-1β production in a murine model of acute gout

Abstract

This study evaluated the role of macrophage migration inhibitory factor in inflammation caused by monosodium urate crystals. The concentration of macrophage migration inhibitory factor was increased in synovial fluid of patients with acute gout, and there was a positive correlation between intra-articular macrophage migration inhibitory factor and IL-1β concentrations. In mice, the injection of monosodium urate crystals into the knee joint increased the levels of macrophage migration inhibitory factor in macrophages and in inflamed tissue. The injection of recombinant macrophage migration inhibitory factor into the joint of mice reproduced the inflammatory response observed in acute gout, including histologic changes, the recruitment of neutrophils, and increased levels of IL-1β and CXCL1. Importantly, the accumulation of neutrophils and the amount IL-1β in the joints were reduced in macrophage migration inhibitory factor-deficient mice when injected with monosodium urate crystals. We observed a similar effect when we blocked macrophage migration inhibitory factor with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid or anti-macrophage migration inhibitory factor. In addition, the blockade of IL-1R and CXCR2 reduced recombinant macrophage migration inhibitory factor-induced neutrophil recruitment. Mechanistically, recombinant macrophage migration inhibitory factor is important for the synthesis of il1β mRNA in vivo and in isolated macrophages. Altogether, macrophage migration inhibitory factor promotes neutrophil accumulation and is important for IL-1β production, which are 2 crucial events contributing to the pathogenesis of acute gout.

Particulate Matter Increases the Severity of Bleomycin-Induced Pulmonary Fibrosis through KC-Mediated Neutrophil Chemotaxis

“…In another treatment test, mice were divided into two groups, receiving vehicle and reparixin, respectively after administration of bleomycin plus PM. Reparixin treatment protocol referred to that described in previous research [32][33][34]. The treatment group received subcutaneous injection of reparixin (30 mg/kg in 100 µL saline-diluted DMSO) (Tocris, Bristol, U.K.) at 30 min before administration of bleomycin and PM, followed by maintenance dose (30 mg/kg in 100 µL saline-diluted DMSO) from day 0 to day 2.…”

Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation

“…Thus, understanding how inflammasome activation is regulated is critical for the development of better treatment strategies. Significantly, one study has demonstrated that MIF is required for IL-1β release and neutrophil recruitment in a mouse model of monosodium urate (MSU) crystal-induced gout 36 , suggesting a possible function of MIF in the regulation of IL-1 in the specific context of NLRP3 activation.…”

Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells

“…Gouty arthritis is characterized by increased hyperuricemia level, which is triggered by disorders of the purine catabolic pathway, and leads to the deposition of monosodium urate (MSU) crystals within synovial joints and tissues. 1 This process of an acute inflammatory attack with intense pain, swelling and skin reddening is highlighted by the influx of neutrophils into articular or periarticular tissues and the release of inflammatory cytokines after the phagocytosis of deposited MSU microcrystals and membranolysis by monocyte–macrophages, 2 which further magnifies the inflammation cascade. The resultant stimulation of inflammatory cytokines is a cardiovascular risk factor, 3 which contributes to the significant damage against human umbilical vein endothelial cells (HUVECs) via an increased apoptosis rate 4 and thrombus formation.…”