Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is involved in inflammatory and immune-mediated diseases but the role of MIF in liver injury has not yet been elucidated. METHODS: We investigated biochemically, histologically and immunologically the character of MIF in concanavalin A (Con A)-induced T-cell-mediated liver injury using MIF knockout (KO) mice and wild-type (WT) mice. RESULTS: MIF KO mice showed significantly decreased serum alanine aminotransferase values and suppressed histological change with massive necrosis of the hepatic parenchymal cells and infiltration of inflammatory cells compared with their WT counterparts. This protection was not mediated by either tumor necrosis factor-alpha or interferon-gamma, which are critical mediators of Con A-induced liver injury, as their serum concentrations were shown to be similar in MIF KO and WT mice. On the other hand, a flow cytometric analysis demonstrated that the number of activated hepatic leukocytes decreased more in the MIF KO mice than in the WT mice. CONCLUSIONS: A lack of MIF protected the mice from Con A-induced liver injury. Controlling the MIF activity may be a useful therapeutic strategy for treating such T-cell activation-associated liver diseases as autoimmune hepatitis and viral hepatitis.     

巨噬细胞移动抑制因子在炎症性肠病发病中的作用

目的: 探讨巨噬细胞移动抑制因子(macrophage migration inhibitory factor, MIF)在炎症性肠病(inflammatory bowel disease, IBD)发病中的意义.方法:2005-03/2007-11广西壮族自治区南溪山医院及外院住院活动期溃疡性结肠炎(ulcerative colitis, UC)患者38例, 克罗恩病(Crohn's disease, CD)患者18例, 其他结肠炎患者23例, 健康体检者20例. ELISA检测受试者血清MIF含量, LAB-SA免疫组化测定肠黏膜组织MIF蛋白表达. 采用胶乳增强免疫透射比浊法检测超敏C-反应蛋白(Hs-CRP).结果: UC、CD及其他结肠炎患者的血清MIF水平均高于正常对照者(10.599±1.895, 8.981±1.409, 8.498±2.242 μg/L vs 5.363±1.841 μg/L; 均P<0.01); hs-CRP阳性的UC患者MIF水平高于hs-CRP阴性的UC患者(11.025±1.863 μg/L vs 9.408±1.485 μg/L, P<0.05), 而hs-CRP阳性的CD患者MIF水平未见显著升高, CD患者的血清MIF水平与其他结肠炎患者的血清MIF水平比较无显著性差异. UC患者的肠黏膜MIF表达与其他结肠炎、CD患者和正常对照者比较, 均具有显著差异(100.00% vs 66.67%, 78.26%, 65.00%; P<0.01).结论:MIF参与溃疡性结肠炎的发病过程, 可能是溃疡性结肠炎活动的指标, 控制MIF的产生可能有治疗作用.     

Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis

OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). METHODS: Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5'-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. RESULTS: A tetranucleotide repeat CATT((5-7)) beginning at nucleotide position -794 and 3 SNPs at positions -173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4-2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type-specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). CONCLUSION: The -173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type-specific regulation of MIF, which may be central to understanding its role in inflammation.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

巨噬细胞迁移抑制因子与疟原虫感染的相关研究进展

疟疾是世界上主要的致死性感染性疾病之一,但是目前药物抗性虫株的出现、有效疫苗的缺乏,特别是对疟原虫生物学、疟疾病理机制以及宿主在疟原虫感染后的免疫应答等方面了解不足是控制疟疾的主要困难.大量研究发现,机体内的巨噬细胞迁移抑制因子(macrophage migration inhibitory factor,MIF)在包括疟疾在内的多种感染性疾病中发挥着重要作用,凶此受到研究者口益广泛的关注.近年来研究者们从疟原虫等寄生虫巾也先后鉴定出MIF分子,它们不仅在结构上具有高等牛物MIF分子的典型特征,而且还具有与之相似的功能.尽管其在感染过程巾的作用尚不清楚,但迄今为止多项研究表明,这些宿主MIF的同源分子具有调节宿主免疫系统的能力.该文综述了宿主MIF和寄生虫MIF在疟疾感染和病理机制中的作用的研究现状.     

The role of macrophage migration inhibitory factor on glucose metabolism and diabetes

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in many inflammatory reactions and disorders, and it has become evident that it also affects glucose homeostasis. The protein is produced by pancreatic beta cells and can promote the release of insulin. It also modulates glucose uptake, glycolysis and insulin resistance in insulin target cells such as the adipocyte, myocyte and cardiomyocyte. Possessing both immunological and endocrinological properties, MIF has been associated with the development of type 1 and type 2 diabetes, and it may be important in the setting of islet transplantation. The present review summarises our current knowledge, based on clinical and research data, on the impact of MIF on both physiological and pathological aspects of glucose metabolism.     

Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pivotal role in several immunoinflammatory and autoimmune diseases. In this study we examined the role of MIF in the development of immunoinflammatory diabetes induced in susceptible strains of mice by multiple low doses of streptozotocin. We found that MIF protein was significantly elevated in islet cells during the development of diabetes, and that targeting MIF activity with either neutralizing antibody or the pharmacological inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester, markedly reduced clinical and histopathological features of the disease, such as hyperglycemia and insulitis. Lymphocytes from mice treated with the MIF inhibitors exhibited reduction of both islet antigen-specific proliferative responses and adhesive cell-cell interactions. Neutralization of MIF also down-regulated the ex vivo secretion of the proinflammatory mediators, TNF-alpha, interferon-gamma, and nitric oxide, while augmenting that of the antiinflammatory cytokine, IL-10. This study provides the first in vivo evidence for a critical role for MIF in the immune-mediated beta-cell destruction in an animal model of human type 1 diabetes mellitus and identifies a new therapeutic strategy for the prevention and treatment of this disease in humans that is based on the selective inhibition of MIF activity.     

The potential role of macrophage migration inhibitory factor on the migration of vascular smooth muscle cells

AIM: Macrophage migration inhibitory factor (MIF) is known as a pro-inflammatory cytokine that regulates a broad spectrum of inflammatory reactions. MIF is expressed in vascular smooth muscle cells (VSMCs), and inhibition of the progression of atherosclerosis was observed in MIF-deficient atherosclerotic mice. However, the functional role of MIF in VSMCs has not been elucidated. The aim of this study was to investigate the role of MIF on the migration of VSMCs. METHODS: Cultured rat A10 cells, derived from rat embryonic aortic smooth muscle cells, were stimulated with oxLDL, and the effect of MIF knockdown on oxLDL-mediated migration of A10 cells was analyzed. RESULTS: Intracellular MIF content was significantly increased and a marked increase of MIF concent-ration was observed in the supernatant of A10 cells treated with oxLDL. The migration of A10 cells was significantly accelerated by the stimulation of recombinant MIF in a dose-dependent manner. Notably, knockdown of intracellular MIF by siRNA abolished oxLDL-induced migration of A10 cells. CONCLUSION: These findings suggest that MIF acts on the migration of VSMCs in an autocrine and paracrine fashion. MIF appears to be a novel target for the prevention of cardiovascular events.     

Evaluation of inflammation and oxidative stress in ankylosing spondylitis: a role for macrophage migration inhibitory factor

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints. Mediators such as macrophage migration inhibitory factor (MIF) and interleukin-10 (IL-10) are thought to be involved in several inflammatory conditions, including AS. Proinflammatory cytokines regulate the production of oxidative stress markers, such as nitric oxide (NO) and malondialdehyde (MDA). Although oxidative stress and lipid peroxidation have been reported in AS, the association of AS with commonly known oxidative stress markers and cytokines remains uncertain. We have therefore studied whether serum MIF levels are elevated in patients with AS and whether the levels correlate with oxidative stress markers and disease activity parameters. Twenty-five AS patients and 18 healthy controls participated in this study; subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. The levels of acute phase reactants, serum levels of glucose, lipids, MIF, IL-10, NO and MDA were studied. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also assessed using with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age and sex distribution were found to be comparable between AS patients and controls (p > 0.05). Acute phase reactants and MIF levels were significantly higher (p < 0.05) and IL-10 levels were significantly lower (<0.001) in the AS patients than in controls. There was a significant correlation between BASMI and MIF levels in AS patients (r = 0.714, p < 0.001). Based on these results, MIF may be involved in the pathogenesis of the chronic inflammation in AS and, consequently, targeting MIF may be beneficial in preventing complications or in initiating early treatment of the disease.