Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

Farr, Laura; Ghosh, Swagata; Moonah, Shannon

doi:10.3389/fimmu.2020.01273

Cited by 116 publications

(118 citation statements)

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“…It is highly involved in the antigen presentation and the activation of CD4 + T cells ( Cresswell, 1994 ). CD74 is the cell surface membrane receptor for the cytokine macrophage migration inhibitory factor (MIF) ( Farr et al, 2020 ). The role of the interaction between CD74 and MIF has been revealed in different types of cancers ( Binsky et al, 2007 ; Nagata et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas

Tang

et al. 2021

Front. Mol. Biosci.

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Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment.Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis.Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival.Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.

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Section: Introductionmentioning

confidence: 99%

CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas

Tang

et al. 2021

Front. Mol. Biosci.

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“…Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine produced by immune cells and non-immune cells ( Bilsborrow et al, 2019 ), play an important role in the inflammatory response and immune regulation ( Calandra and Bucala, 1997 ; Burger et al, 2002 ). Ample evidence shows that MIF is involved in the regulation of heart function under pathological conditions, including burns, diabetes and I/RI ( Pohl et al, 2016 ; Yu et al, 2019 ; Farr et al, 2020 ). Studies have also confirmed that MIF plays a crucial role in myocardial protection by ischemic preconditioning ( Ruze et al, 2019 ), Ischemic preconditioning activates RISK and AMPK signal pathways through MIF, reduced myocardial infarction area and cardiomyocyte apoptosis ( Dow et al, 2012 ; Emontzpohl et al, 2019 ), inhibition of ROS production ( Yang et al, 2010 ) and inflammatory infiltration of cells, maintained endothelial cell function ( Argaud et al, 2005 ), thereby improving cardiac dysfunction caused by myocardial I/RI ( Vinten-Johansen et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway

Hou

et al. 2021

Front. Pharmacol.

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Subject: Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions.Methods: H9c2 cardiomyocytes were cultured in normal and high-concentration glucose medium to establish a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes. SPostC was performed with 2.4% sevoflurane for 15 min before reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis; Testing cell energy metabolism by detecting reactive oxygen species (ROS) generation, ATP content and mitochondrial membrane potential; Analysis of the change of HIF-1α, MIF and AMPKα mRNA expression by RT-PCR. Western blotting was used to examine the expression of HIF-1α, MIF, AMPKα and p-AMPKα proteins. HIF-1α and MIF inhibitors and agonists were administered 40 min before hypoxia.Results: 1) SPostC exerts a protective effect by increasing cell viability, reducing LDH levels and cell apoptosis under low glucose (5 μM) after undergoing H/R injury; 2) High glucose concentration (35 μM) eliminated the cardioprotective effect of SPostC, which is manifested by a significantly decrease in the protein and mRNA expression level of the HIF-1α/MIF/AMPK signaling pathway, accompanied by decreased cell viability, increased LDH levels and apoptosis, increased ROS production, decreased ATP synthesis, and decreased mitochondrial membrane potential; 3. Under high glucose (35 μM), the expression levels of HIF-1α and MIF were up-regulated by using agonists, which can significantly increase the level of p-AMPKα protein, and the cardioprotective effect of SPostC was restored.Conclusion: The signal pathway of HIF-1α/MIF/AMPK of H9c2 cardiomyocytes may be the key point of SPostC against H/R injure. The cardioprotective of SPostC could be restored by upregulating the protein expression of HIF-1α and MIF under hyperglycemia.

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“…We are not currently able to determine whether the inverse correlation of MIF and inflammation represents an epiphenomenon, associated to the wound healing processes that follow the acute inflammatory phases, or whether MIF actually takes place in regulating inflammation in the skin. It is of interest in this setting that recent evidences indicate a key role of the MIF/CD74 cell signaling pathway in regulating wound healing after injury [ 37 ]. However, it should also be noticed that MIF is mainly produced byTh2 cells, rather that Th1 cells [ 38 ], hence, it may take a role in the resolution phase of the disease.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

et al. 2021

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Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

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Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

Cited by 116 publications

References 108 publications

CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas

CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas

Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

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