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Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes.

Abstract：

OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium has never been reported. The goal of this study is to examine MIF in the myocardium. METHODS AND RESULTS:MIF protein and mRNA levels were assayed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Increased MIF concentrations were detected in the sera of patients with acute myocardial infarction (AMI). In cultured rat cardiac myocytes, significant amounts of MIF were produced in response to hypoxia and hydrogen peroxide (H(2)O(2)), but not to angiotensin II, endothelin-1, interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha). H(2)O(2)-induced MIF production increased in a time- and dose-dependent manner and was completely abolished in the presence of catalase. H(2)O(2) also induced MIF mRNA expression. The H(2)O(2)-induced MIF production was completely inhibited by the protein kinase C (PKC) inhibitor GF109203X, partially inhibited by the tyrosine kinase inhibitor herbimycin A, and uninhibited by calcium chelation or phorbol ester-sensitive PKC down-regulation. This suggests that H(2)O(2)-induced MIF production is mediated by an atypical PKC isoform. DNA microarray analysis revealed that 52 genes were preferentially expressed in response to MIF. Of these, the MIF-induced expression of both glutathione S-transferase (GST) and lipopolysaccharide-induced CXC chemokine (LIX) mRNAs was confirmed using RT-PCR analysis. CONCLUSION:The present results suggest that MIF is expressed by the myocardium in response to redox stress and may play a role in the pathogenesis of myocardial ischemia.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Takahashi M,Nishihira J,Shimpo M,Mizue Y,Ueno S,Mano H,Kobayashi E,Ikeda U,Shimada K

doi

10.1016/s0008-6363(01)00408-4

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

438-45

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636301004084

journal_volume

pub_type

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Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes.