Dataset Information

The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.

ABSTRACT:

Introduction

Anesthetic-induced preconditioning (AIP) is known to elicit cardioprotective effects that are mediated at least in part by activation of the kinases AMPK and PKC? as well as by inhibition of JNK. Recent data demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor (MIF) provides cardioprotection through activation and/or inhibition of kinases that are also known to mediate effects of AIP. Therefore, we hypothesized that MIF could play a key role in the AIP response.

Methods

Cardiomyocytes were isolated from rats and subjected to isoflurane preconditioning (4 h; 1.5 vol. %). Subsequently, MIF secretion and alterations in the activation levels of protective kinases were compared to a control group that was exposed to ambient air conditions. MIF secretion was quantified by ELISA and AIP-induced activation of protein kinases was assessed by Western blotting of cardiomyocyte lysates after isoflurane treatment.

Results

In cardiomyocytes, preconditioning with isoflurane resulted in a significantly elevated secretion of MIF that followed a biphasic behavior (30 min vs. baseline: p = 0.020; 24 h vs. baseline p = 0.000). Moreover, quantitative polymerase chain reaction demonstrated a significant increase in MIF mRNA expression 8 h after AIP. Of note, activation of AMPK and PKC? coincided with the observed peaks in MIF secretion and differed significantly from baseline.

Conclusions

These results suggest that the pleiotropic mediator MIF is involved in anesthetic-induced preconditioning of cardiomyocytes through stimulation of the protective kinases AMPK and PKC?.

SUBMITTER: Goetzenich A

PROVIDER: S-EPMC3965449 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.

Goetzenich Andreas A Kraemer Sandra S Rossaint Rolf R Bleilevens Christian C Dollo Florian F Siry Laura L Rajabi-Alampour Setareh S Beckers Christian C Soppert Josefin J Lue Hongqi H Rex Steffen S Bernhagen Jürgen J Stoppe Christian C

PloS one 20140325 3

<h4>Introduction</h4>Anesthetic-induced preconditioning (AIP) is known to elicit cardioprotective effects that are mediated at least in part by activation of the kinases AMPK and PKCε as well as by inhibition of JNK. Recent data demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor (MIF) provides cardioprotection through activation and/or inhibition of kinases that are also known to mediate effects of AIP. Therefore, we hypothesized that MIF could play a key role in t ...[more]

PMID: 24667295

Similar Datasets

Project description:ObjectiveTo examine the association between macrophage migration inhibitory factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA) in human subjects, and to assess the role of MIF in a murine model of granulomatous vasculitis.MethodsThe human study involved 1,077 patients with GPA and healthy controls whose serum was genotyped by capillary electrophoresis for the MIF -794 CATT5-8 promoter microsatellite (rs5844572). MIF promoter, CATT-length-dependent gene expression in response to β-glucan was assessed by gene reporter assays. In mouse studies, granulomatous disease was induced by injection of Candida albicans β-glucan into wild-type (WT) or Mif-knockout (Mif-KO) C57BL/6 mice and C57BL/6 mice transgenically overexpressing Mif in lung epithelium (Mif lung-Tg2.1). Mice were treated with a neutralizing anti-MIF antibody and analyzed for the density of pulmonary granulomas, expression of inflammatory chemokines, and frequency of mortality.ResultsThe percentage of human subjects carrying >5 CATT repeats in each MIF allele (high genotypic MIF expressers) was 60.2% among patients with GPA and 53.9% among healthy controls (adjusted P = 0.049). In response to granulomatous stimulation, human MIF gene expression increased proportionally with CATT length. Mif lung-Tg2.1 mice exhibited more pulmonary granulomas than WT mice, which in turn showed more granulomas than Mif-KO mice. A significantly higher percentage of Mif lung-Tg2.1 mice, compared to Mif-KO or WT mice, died when injected with Candida albicans β-glucan, and treatment of these mice with an anti-MIF monoclonal antibody protected against a lethal outcome. Levels of MIF-dependent neutrophil/macrophage chemokines were elevated in the bronchoalveolar lavage fluid or plasma of Mif lung-Tg2.1 mice.ConclusionPatients with GPA have an increased frequency of high MIF expression CATT alleles. Higher Mif expression increases the incidence of mortality and pulmonary granulomas in Mif lung-Tg2.1 mice, while anti-MIF treatment protects these mice against death. Blockade of MIF in high genotypic MIF expressers may therefore offer a selective pharmacologic therapy for GPA.

Project description:BackgroundOsteoarthritis (OA) is the most prevalent form of arthritis and the major cause of disability and overall diminution of quality of life in the elderly population. Currently there is no cure for OA, partly due to the large gaps in our understanding of its underlying molecular and cellular mechanisms. Macrophage migration inhibitory factor (MIF) is a procytokine that mediates pleiotropic inflammatory effects in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, data on the role of MIF in OA is limited with conflicting results. We undertook this study to investigate the role of MIF in OA by examining MIF genotype, mRNA expression, and protein levels in the Newfoundland Osteoarthritis Study.MethodsOne hundred nineteen end-stage knee/hip OA patients, 16 RA patients, and 113 healthy controls were included in the study. Two polymorphisms in the MIF gene, rs755622, and -794 CATT5-8, were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR followed by automated capillary electrophoresis, respectively. MIF mRNA levels in articular cartilage and subchondral bone were measured by quantitative polymerase chain reaction. Plasma concentrations of MIF, tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), and interleukin-1 beta (IL-1?) were measured by enzyme-linked immunosorbent assay.Resultsrs755622 and -794 CATT5-8 genotypes were not associated with MIF mRNA or protein levels or OA (all p???0.19). MIF mRNA level in cartilage was lower in OA patients than in controls (p?=?0.028) and RA patients (p?=?0.004), while the levels in bone were comparable between OA patients and controls (p?=?0.165). MIF protein level in plasma was lower in OA patients than in controls (p?=?3.01?×?10-10), while the levels of TNF-?, IL-6 and IL-1? in plasma were all significantly higher in OA patients than in controls (all p???0.0007). Multivariable logistic regression showed lower MIF and higher IL-1? protein levels in plasma were independently associated with OA (OR per SD increase?=?0.10 and 8.08; 95% CI?=?0.04-0.19 and 4.42-16.82, respectively), but TNF-? and IL-6 became non-significant.ConclusionsReduced MIF mRNA and protein expression in OA patients suggested MIF might have a protective role in OA and could serve as a biomarker to differentiate OA from other joint disorders.

Dataset Information

The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.

Introduction

Methods

Results

Conclusions

Publications

The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets