The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

Okamoto, Tamami; Atsumi, T; Shimizu, Chisato; Yoshioka, Narihito; Koike, Takao

doi:10.5551/jat.e495

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…to 24 hrs). MIF release reached levels of up to 30 ng/ml and was thus comparable to secreted MIF levels observed previously following cell stimulation with endotoxin or inflammatory cytokines [29,30]. It should be noted that the time-point t ϭ 0 hr, due to handling delays and cell stress related to hypoxic medium change, was not a true 0 min.…”

Section: Hypoxia-induced Secretion Of Mif By Huvecssupporting

confidence: 82%

Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment

Simons

Grieb

Hristov

et al. 2010

Journal of Cellular and Molecular Medicine

125

106

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Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine that was recently identified as a non-cognate ligand of the CXC-family chemokine receptors 2 and 4 (CXCR2 and CXCR4). MIF is expressed and secreted from endothelial cells (ECs) following atherogenic stimulation, exhibits chemokine-like properties and promotes the recruitment of leucocytes to atherogenic endothelium. CXCR4 expressed on endothelial progenitor cells (EPCs) and EC-derived CXCL12, the cognate ligand of CXCR4, have been demonstrated to be critical when EPCs are recruited to ischemic tissues. Here we studied whether hypoxic stimulation triggers MIF secretion from ECs and whether the MIF/CXCR4 axis contributes to EPC recruitment. Exposure of human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAoECs) to 1% hypoxia led to the specific release of substantial amounts of MIF. Hypoxia-induced MIF release followed a biphasic behaviour. MIF secretion in the first phase peaked at 60 min. and was inhibited by glyburide, indicating that this MIF pool was secreted by a non-classical mechanism and originated from pre-formed MIF stores. Early hypoxia-triggered MIF secretion was not inhibited by cycloheximide and echinomycin, inhibitors of general and hypoxia-inducible factor (HIF)-1α-induced protein synthesis, respectively. A second phase of MIF secretion peaked around 8 hrs and was likely due to HIF-1α-induced de novo synthesis of MIF. To functionally investigate the role of hypoxia-inducible secreted MIF on the recruitment of EPCs, we subjected human AcLDL+ KDR+ CD31+ EPCs to a chemotactic MIF gradient. MIF potently promoted EPC chemotaxis in a dose-dependent bell-shaped manner (peak: 10 ng/ml MIF). Importantly, EPC migration was induced by supernatants of hypoxia-conditioned HUVECs, an effect that was completely abrogated by anti-MIF- or anti-CXCR4-antibodies. Thus, hypoxia-induced MIF secretion from ECs might play an important role in the recruitment and migration of EPCs to hypoxic tissues such as after ischemia-induced myocardial damage.

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Section: Hypoxia-induced Secretion Of Mif By Huvecssupporting

confidence: 82%

Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment

Simons

Grieb

Hristov

et al. 2010

Journal of Cellular and Molecular Medicine

125

106

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“…In addition to proliferation of VSMCs within the vessel wall, the migration of VSMCs from the media into the neointima is another important feature in the pathogenesis of atherosclerosis [5,32,33]. This process is regulated by multiple factors, and MIF is one of the multiple factors that could increase VSMCs migration[33].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…This process is regulated by multiple factors, and MIF is one of the multiple factors that could increase VSMCs migration[33]. MIF is an important mediator of vessel wall remodeling and acts on the migration of VSMCs in an autocrine and paracrine manner[33]. Previous report shows that hypoxia induces the migration of human coronary artery smooth muscle cells, and the migration is elicited by thrombospondin-1[34].…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1α dependent pathway

Luo

Yang

et al. 2010

BMC Cell Biol

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BackgroundHypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time.ResultsExpression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs.ConclusionOur results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1α activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1α mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation.

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“…Nonetheless, MIF clearly induces adhesion and migration of monocyte-lineage cells in postcapillary venules, and that function is mediated by the chemokine CCL2 (MCP-1), which is induced in ECs by MIF, itself [44]. In addition, expression and secretion of MIF by vascular smooth muscle cells (VSMCs) is increased when the cells are stimulated with oxidized low-density lipoprotein, and recombinant MIF enhances the migration of VSMCs [45]. This suggests that MIF acts in an autocrine and paracrine fashion to modulate the migration of VSMCs, and may be associated with the development of advanced lesions during the course of atherogenesis.…”

Section: Biological Activities Of Mifmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor: A Multifunctional Cytokine in Rheumatic Diseases

et al. 2010

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Macrophage migration inhibitory factor (MIF) was originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibited the random migration of macrophages. MIF is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses. Moreover, the pivotal nature of its involvement highlights the importance of MIF to the pathogenesis of various inflammatory disorders and suggests that blocking MIF may be a useful therapeutic strategy for treating these diseases. This paper discusses the function and expressional regulation of MIF in several rheumatic diseases and related conditions.

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The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

Cited by 7 publications

References 32 publications

Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment

Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment

Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1α dependent pathway

Macrophage Migration Inhibitory Factor: A Multifunctional Cytokine in Rheumatic Diseases

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