title: 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.
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Izabela
authors: I
authors: Galvão
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Ana Carolina Fialho
authors: AC
authors: Dias
authors: Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Livia Duarte
authors: LD
authors: Tavares
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Irla Paula Stopa
authors: IP
authors: Rodrigues
authors: Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Celso Martins
authors: CM
authors: Queiroz-Junior
authors: Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Vivian Vasconcelos
authors: VV
authors: Costa
authors: Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Alesandra Corte
authors: AC
authors: Reis
authors: Division of Rheumatology, School of Medicine of Ribeirao Preto, Universidade de São Paulo, Brazil.
authors: Rene Donizeti
authors: RD
authors: Ribeiro Oliveira
authors: Division of Rheumatology, School of Medicine of Ribeirao Preto, Universidade de São Paulo, Brazil.
authors: Paulo
authors: P
authors: Louzada-Junior
authors: Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Daniele Glória
authors: DG
authors: Souza
authors: Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, New Haven, Connecticut, USA.
authors: Lin
authors: L
authors: Leng
authors: Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, New Haven, Connecticut, USA.
authors: Richard
authors: R
authors: Bucala
authors: Department of Clinical Analysis and Toxicological, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Lirlândia Pires
authors: LP
authors: Sousa
authors: Laboratory of Inflammation and Immunity, Department of Immunology, Institute of Microbiology, Universidade Federal do Rio de Janeiro, Brazil.
authors: Marcelo Torres
authors: MT
authors: Bozza
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil mmtex@icb.ufmg.br.
authors: Mauro Martins
authors: MM
authors: Teixeira
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil famaral@icb.ufmg.br.
authors: Flávio Almeida
authors: FA
authors: Amaral
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006073:Gout / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007267:Injections; D053583:Interleukin-1beta / Q000096:biosynthesis*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D014527:Uric Acid / Q000008:administration & dosage
chemical_list: D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; D014527:Uric Acid
keywords: MIF; arthritis; chemokine; inflammasome