scholarly journals Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Robert Kleemann ◽  
Richard Bucala
Keyword(s):  
Insulin Resistance ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Current Knowledge ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Low Grade ◽  
Macrophage Migration ◽  
Animal Models Of Disease ◽  
Models Of Disease

Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF) is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

scholarly journals Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

2012 ◽  
Vol 71 (4) ◽  
pp. 622-633 ◽  
Author(s):  
Orla M. Finucane ◽  
Clare M. Reynolds ◽  
Fiona C. McGillicuddy ◽  
Helen M. Roche
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Metabolic Diseases ◽  
Inhibitory Factor ◽  
Low Grade ◽  
Macrophage Migration ◽  
Pharmacological Agents

High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

scholarly journals Critical Role of Macrophage Migration Inhibitory Factor Activity in Experimental Autoimmune Diabetes

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2942-2951 ◽  
Author(s):  
Ivana Cvetkovic ◽  
Yousef Al-Abed ◽  
Djordje Miljkovic ◽  
Danijela Maksimovic-Ivanic ◽  
Jesse Roth ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Autoimmune Diabetes ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Factor Activity ◽  
Experimental Autoimmune

Critical role of macrophage migration inhibitory factor in sepsis via interfere with MCP-1/CCL2 signaling pathway

2015 ◽  
Vol 3 (3) ◽  
pp. 215-228
Author(s):  
Jason J Goodman ◽  
Alison A Putensen
Keyword(s):  
Adhesion Molecule ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Bacterial Infections ◽  
Critical Role ◽  
Cecal Ligation ◽  
Inhibitory Factor ◽  
Intercellular Adhesion Molecule ◽  
Macrophage Migration

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by the multiple cell types, modulates the expression of several inflammatory molecules. Since MIF is a critical mediator of septic shock by modulation of innate immune responses and many studies demonstrated the role of MIF in sepsis pathogenesis and signaling pathways; however, the mechanisms underlying these changes remain unclear. MIF also promotes the migration and recruitment of immune cells inducing the expression of chemokines (monocyte chemoattractant protein (MCP)-1, adhesion molecules as intercellular adhesion molecule (I-CAM)-1 and vascular cell adhesion molecule (V-CAM)-1. Male MIF+/+ and MIF−/− mice were subjected to cecal ligation and puncture (CLP) to induce sepsis. Mif(-/-) mice had enhanced susceptibility to bacterial infections and impaired tumor necrosis factor (TNF) compared with MIF+/+. Further, Mif(-/-) mice showed upregulation of proinflammatory cytokine and eleveated the levels of MCP-1. Interesting treatment with recombinant human MIF (rhMIF) before CLP protected the animals from sepsis. Together, these data suggest that potential of targeting or exploiting MIF for therapeutic strategies in the management of sepsis.

The critical role of macrophage migration inhibitory factor in insulin activity

Cytokine ◽  
2014 ◽  
Vol 69 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Milica Vujicic ◽  
Lidija Senerovic ◽  
Ivana Nikolic ◽  
Tamara Saksida ◽  
Stanislava Stosic-Grujicic ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Insulin Activity

scholarly journals A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia

2006 ◽  
Vol 203 (5) ◽  
pp. 1185-1196 ◽  
Author(s):  
Michael A. McDevitt ◽  
Jianlin Xie ◽  
Shanmugasundaram Ganapathy-Kanniappan ◽  
Jason Griffith ◽  
Aihua Liu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Malaria Infection ◽  
Macrophage Migration Inhibitory Factor ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Migration ◽  
Erythroid Progenitor ◽  
Malarial Anemia

The pathogenesis of malarial anemia is multifactorial, and the mechanisms responsible for its high mortality are poorly understood. Studies indicate that host mediators produced during malaria infection may suppress erythroid progenitor development (Miller, K.L., J.C. Schooley, K.L. Smith, B. Kullgren, L.J. Mahlmann, and P.H. Silverman. 1989. Exp. Hematol. 17:379–385; Yap, G.S., and M.M. Stevenson. 1991. Ann. NY Acad. Sci. 628:279–281). We describe an intrinsic role for macrophage migration inhibitory factor (MIF) in the development of the anemic complications and bone marrow suppression that are associated with malaria infection. At concentrations found in the circulation of malaria-infected patients, MIF suppressed erythropoietin-dependent erythroid colony formation. MIF synergized with tumor necrosis factor and γ interferon, which are known antagonists of hematopoiesis, even when these cytokines were present in subinhibitory concentrations. MIF inhibited erythroid differentiation and hemoglobin production, and it antagonized the pattern of mitogen-activated protein kinase phosphorylation that normally occurs during erythroid progenitor differentiation. Infection of MIF knockout mice with Plasmodium chabaudi resulted in less severe anemia, improved erythroid progenitor development, and increased survival compared with wild-type controls. We also found that human mononuclear cells carrying highly expressed MIF alleles produced more MIF when stimulated with the malarial product hemozoin compared with cells carrying low expression MIF alleles. These data suggest that polymorphisms at the MIF locus may influence the levels of MIF produced in the innate response to malaria infection and the likelihood of anemic complications.

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