Dataset Information

Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells.

ABSTRACT: Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coronary artery ECs under different shear stress, we found that athero-protective LS attenuates the expression of MIF whereas pro-atherosclerotic oscillatory shear stress (OS) significantly increased the expression of MIF. En face staining of rabbit aorta revealed high MIF immunoreactivity in lesser curvature as well as arterial bifurcation areas where OS is predominant. Mechanistically, we found that Krüpple like factor 2 (KLF2) is required for inhibition of MIF expression in ECs in the context of shear stress. Knockdown of KLF2 abolishes LS-dependent MIF inhibition while overexpression of KLF2 significantly attenuated MIF expression. Overall, the present work showed that MIF is a shear stress-sensitive cytokine and is transcriptionally regulated by KLF2, suggesting that LS exerts its athero-protective effect in part by directly inhibiting pro-inflammatory MIF expression.

SUBMITTER: Qiao C

PROVIDER: S-EPMC5799263 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells.

Qiao Congzhen C Li Shengdi S Lu Haocheng H Meng Fan F Fan Yanbo Y Guo Yanhong Y Chen Y Eugene YE Zhang Jifeng J

Scientific reports 20180205 1

Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coron ...[more]

PMID: 29403061

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Project description:AimTo investigate the expression of macrophage migration inhibitory factor (MIF) and detect its role in the innate immune response of fungal keratitis (FK).MethodsWe collected the paraffin-embedded cornea tissues from 10 FK and 6 ocular trauma patients to explore the MIF expression by immunohistochemistry. Then we cultured telomease-immortalized human corneal epithelial cells (THCEs), stimulated by the hyphae suspension of Aspergillus fumigatus (A. fumigatus) to detect the change of MIF with or without the pretreatment of MIF inhibitor [4-Iodo-6-phenylpyrimidine (4-IPP)] by real-time polymerase chain reaction (PCR). The protein level of MIF was also tested by immunohistochemistry, and the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA were compared between normal, hyphae stimulated and 4-IPP pretreated groups by real-time PCR to study the influence of MIF on the expression of TNF-α and IL-6. Corneal severity of rats' FK models was documented by clinical scores, and real-time PCR. Western blot and immunohistochemistry were used to test the expression of MIF, TNF-α and IL-6 in rats' corneas.ResultsIn the corneas of FK patients, there was much stronger expression of MIF than that in the normal group showed by immunohistochemistry. In cultured THCEs stimulated by A. fumigatus, the expression of MIF became stronger in both immunohistochemistry and PCR at 16, 24, 32 and 48h post infection (p.i.; P<0.01, P<0.01, P<0.01, P<0.05). After pretreated with 4-IPP, the expression of MIF reduced at 4, 8, 16h p.i. (P<0.05, P<0.05, P<0.05) and the downstream TNF-α and IL-6 decreased obviously (P<0.05, P<0.01). In rats with A. fumigatus keratitis, the relative mRNA and protein level of MIF increased than those in the normal group by PCR (at 1d: P<0.01, 3d: P<0.01, 5d: P<0.01), Western blot and immunohistochemistry. After blocked MIF with 4-IPP, the clinical outcomes of rat keratitis showed markedly reduced inflammatory response (P<0.01), with TNF-α and IL-6 decreased in accordance with those in THCEs by PCR (P<0.05, P<0.01).ConclusionThe expression of MIF increased significantly in FK patients, THCEs and rats stimulated by A. fumigatus. After blocked with 4-IPP, the expression of MIF reduced, and so did its downstream cytokines: TNF-α and IL-6. The inflammation reaction of the rats' corneas lightened after pretreated with 4-IPP. MIF may play a role in the innate immune response of the corneal resistance against A. fumigatus.

Project description:Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.

Dataset Information

Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells.

Publications

Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells.

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