Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

Willis, Monte S.; Carlson, Deborah; DiMaio, J. Michael; White, Michael; White, D. Jean; Adams, Glenn A.; Horton, Jureta W.; Giroir, Brett P.

doi:10.1152/ajpheart.00189.2004

Cited by 52 publications

(32 citation statements)

References 54 publications

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“…However, MIF is also expressed in several tissues, including the heart, in which it has a physiologic role during ischemia (29). The current results indicate that endogenous cardiac MIF inhibits activation of the JNK pathway and limits myocardial reperfusion injury after ischemia.…”

Section: Discussionmentioning

confidence: 53%

Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion

Qi¹,

Hu²,

Wu³

et al. 2009

J. Clin. Invest.

167

172

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that also modulates physiologic cell signaling pathways. MIF is expressed in cardiomyocytes and limits cardiac injury by enhancing AMPK activity during ischemia. Reperfusion injury is mediated in part by activation of the stress kinase JNK, but whether MIF modulates JNK in this setting is unknown. We examined the role of MIF in regulating JNK activation and cardiac injury during experimental ischemia/reperfusion in mouse hearts. Isolated perfused Mif -/-hearts had greater contractile dysfunction, necrosis, and JNK activation than WT hearts, with increased upstream MAPK kinase 4 phosphorylation, following ischemia/reperfusion. These effects were reversed if recombinant MIF was present during reperfusion, indicating that MIF deficiency during reperfusion exacerbated injury. Activated JNK acts in a proapoptotic manner by regulating BCL2-associated agonist of cell death (BAD) phosphorylation, and this effect was accentuated in Mif -/-hearts after ischemia/reperfusion. Similar detrimental effects of MIF deficiency were observed in vivo following coronary occlusion and reperfusion in Mif -/-mice. Importantly, excess JNK activation also was observed after hypoxia-reoxygenation in human fibroblasts homozygous for the MIF allele with the lowest level of promoter activity. These data indicate that endogenous MIF inhibits JNK pathway activation during reperfusion and protects the heart from injury. These findings have clinical implications for patients with the low-expression MIF allele.

show abstract

Section: Discussionmentioning

confidence: 53%

Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion

Qi¹,

Hu²,

Wu³

et al. 2009

J. Clin. Invest.

167

172

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that MIF is expressed in the myocardium (11,16) and that MIF neutralization by anti-MIF antibody reversed endotoxin or burn injury-induced cardiac dysfunction (11,50). Anti-MIF treatment also protected TNF-␣ knockout mice, which were sensitive to CLP and succumbed quickly to uncontrolled infection from lethal peritonitis induced by CLP (11).…”

Section: Discussionmentioning

confidence: 99%

Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice

Ha¹,

Fang²,

Grant³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice. Am J Physiol Heart Circ Physiol 291: H1910 -H1918, 2006. First published June 9, 2006 doi:10.1152/ajpheart.01264.2005.-Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. We have previously reported that glucan phosphate (GP) significantly increased survival in a murine model of cecal ligation and puncture (CLP)-induced sepsis. In the present study, we examined the effect of GP on cardiac dysfunction in CLP-induced septic mice. GP was administered to ICR/HSD mice 1 h before induction of CLP. Sham surgically operated mice served as control. Cardiac function was significantly decreased 6 h after CLP-induced sepsis compared with sham control. In contrast, GP administration prevented CLPinduced cardiac dysfunction. Macrophage migration inhibitory factor (MIF) has been implicated as a major factor in cardiomyocyte apoptosis and cardiac dysfunction during septic shock. CLP increased myocardial MIF expression by 88.3% (P Ͻ 0.05) and cardiomyocyte apoptosis by 7.8-fold (P Ͻ 0.05) compared with sham control. GP administration, however, prevented CLP-increased MIF expression and decreased cardiomyocyte apoptosis by 51.2% (P Ͻ 0.05) compared with untreated CLP mice. GP also prevented sepsis-caused decreases in phospho-Akt, phospho-GSK-3␤, and Bcl-2 levels in the myocardium of septic mice. These data suggest that GP treatment attenuates cardiovascular dysfunction in fulminating sepsis. GP administration also activates the phosphoinositide 3-kinase/Akt pathway, decreases myocardial MIF expression, and reduces cardiomyocyte apoptosis.

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“…79 Similarly, MIF has been shown to mediate the late and prolonged cardiac depression after burn injury associated with major tissue damage that was restored by anti-MIF treatment. 80 Notably, an increase in MIF within the alveolar space during late experimental sepsis or MIF instilled exogenously into the lungs induced kinase activation and phosphorylation in the heart, eg, of MAPK, as indicative of myocardial depression, suggesting that MIF released from the lungs during sepsis may in part be responsible for the cardiac dysfunction accompanying sepsis. 81 A crucial role of MIF also has been revealed in the pathogenesis of experimental autoimmune myocarditis, as shown by antibody neutralization, which inhibited the onset and reduced the severity of disease in a therapeutic setting.…”

Section: Mif Contributes To Myocardial Dysfunction and Sepsismentioning

confidence: 99%

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

2008

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Abstract-The highly conserved and archetypical yet atypical cytokine macrophage migration inhibitory factor (MIF) fulfills pleiotropic immune functions in many acute and chronic inflammatory diseases. Recent evidence has emerged from both expression and functional studies to implicate MIF in various aspects of cardiovascular disease. The present review is aimed at providing a synopsis of the involvement of MIF in the inflammatory pathogenesis of atherosclerosis and its consequences, namely unstable plaque formation, remodeling after arterial injury, aneurysm formation, myocardial infarction, or ischemia-reperfusion injury. In addition, other forms of myocardial dysfunction and inflammation and the role of MIF in angiogenesis are reviewed. The functional data are reconciled with recent progress in the identification of heptahelical (CXC chemokine) receptors for MIF, its prototypic role as their noncanonical ligand, and its signal transduction profile operative in atherogenic and inflammatory recruitment of mononuclear cells and in the oxidative damage and apoptosis of cardiomyocytes. Its unique features and functions clearly distinguish MIF from other cytokines implicated in atherogenesis and make it a prime target for achieving therapeutic regression of atherosclerosis.

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Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

Abstract: . Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury.

Cited by 52 publications

References 54 publications

Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion

Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion

Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice

Macrophage Migration Inhibitory Factor in Cardiovascular Disease

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