Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion (J Clin Invest, 2009, 119:3807-3816)

報告日期: 2010/04/13
報告時間: 16:00/16:50
報告學生: 莊淵州
講評老師: 何中良
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990413-2.pdf

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

Dake Qi, Xiaoyue Hu, Xiaohong Wu, Melanie Merk, Lin Leng, Richard Bucala, and Lawrence H. Young

J. Clin. Invest.119:3807–3816(2009)

 

StudentChuang, Yuan-Chou

CommentatorDr. Ho, Chung-Liang

Time2010/04/13  4:10 P.M.

PlaceRoom 602

 

Abstract:

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine which plays important roles in many different diseases[1]. Functional abolishment of MIF increases the survival rate of sepsis, west nile virus and dengue virus infections in mice. In addition, MIF can up-regulate the AMP-activated protein kinase (AMPK) to protect the heart function of mice in ischemia [2]. MIF can regulate another kinase JNK. However, the relationship of MIF and JNK during ischemia is still unknown. In this study, the author assessed the effects of MIF on JNK activation during ischemia/reperfusion (IR) using MIF knockout (MIF-/-) mice. They found WT mice shows less MAPK kinase 4 (MKK4) and JNK phosphorylation, higher left ventricle (LV) pressure, and decreased infarct area as compared to MIF-/- mice during IR. Injection of recombinant MIF during reperfusion in MIF-/- mice could inhibit JNK and MKK4 phosphorylation. Using JNK inhibitor SP600215, they found infract area and apoptotic cells were decreased whereas BCL2-associated agonist of cell death (BAD) phosphorylation and LV pressure were increased. Last but not least, they found JNK activation were higher in human fibroblasts with the low expression 5-CATT repeat allele during hypoxia-reoxygenation. These results indicate that endogenous MIF inhibits MKK4/JNK activation which may contributes to protect heart function during IR. Patients with a low-MIF-expression genotype may be more susceptible to myocardial injury and JNK inhibitor might be an effective treatment to prevent heart injury in these patients

 

Reference:

1.   Calandra, T. and T. Roger, Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol, 2003. 3(10): p. 791-800.

2.   Miller, E.J., et al., Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature, 2008. 451(7178): p. 578-82.