scholarly journals Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma

2019 ◽  
Vol 9 (10) ◽  
pp. 284 ◽  
Author(s):  
Eugenio Cavalli ◽  
Emanuela Mazzon ◽  
Santa Mammana ◽  
Maria Basile ◽  
Salvo Lombardo ◽  
...  
Keyword(s):  
T Cells ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Cytotoxic T Cells ◽  
Hdac Inhibitors ◽  
Inhibitory Factor ◽  
Mycn Amplification ◽  
Macrophage Migration ◽  
Dopachrome Tautomerase

Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts several overlapping functions with MIF. Growing evidence suggests a key role for MIF and DDT in the development of cancer. The aim of this study is to characterize the prognostic value of MIF and DDT in NB. We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification. Moreover, higher levels of MIF are mostly enriched by Th1 cells, while lower levels of MIF are associated with an increased proportion of B cells, Cytotoxic T cells, Dendritic cells and Natural Killer T cells. We also show that treatment with the histone deacetylase (HDAC) inhibitor, vorinostat, of the NB cell line, SH-SY5Y, determines a significant reduction in the expression of both MIF and DDT. Finally, MIF and DDT inhibition by short interfering RNA is able to revert vincristine sensitivity in vitro. Overall, our data suggest that MIF exert pro-tumorigenic properties in NB, likely by dampening antigen presentation and cytotoxic immune responses, and we propose the HDAC inhibitors as a potential therapeutic strategy for NB patients.

scholarly journals Upregulated Expression of Macrophage Migration Inhibitory Factor, Its Analogue D-Dopachrome Tautomerase, and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 667 ◽  
Author(s):  
Cavalli ◽  
Mazzon ◽  
Basile ◽  
Mangano ◽  
Di Marco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Migration Inhibitory Factor ◽  
Cd4 T Cells ◽  
Macrophage Migration Inhibitory Factor ◽  
Clinically Isolated Syndrome ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Healthy Controls ◽  
Dopachrome Tautomerase

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.

scholarly journals Oxygen regulation of macrophage migration inhibitory factor in human placenta

2007 ◽  
Vol 292 (1) ◽  
pp. E272-E280 ◽  
Author(s):  
Francesca Ietta ◽  
Yuanhong Wu ◽  
Roberta Romagnoli ◽  
Nima Soleymanlou ◽  
Barbara Orsini ◽  
...  
Keyword(s):  
High Altitude ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Extravillous Trophoblast ◽  
Macrophage Migration ◽  
Low Oxygen ◽  
Placental Development

Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine involved in regulation of macrophage function. In addition, MIF may also play a role in murine and human reproduction. Although both first trimester trophoblast and decidua express MIF, the regulation and functional significance of this cytokine during human placental development remains unclear. We assessed MIF expression throughout normal human placental development, as well as in in vitro (chorionic villous explants) and in vivo (high altitude placentae) models of human placental hypoxia. Dimethyloxalylglycine (DMOG), which stabilizes hypoxia inducible factor-1 under normoxic conditions, was also used to mimic the effects of hypoxia on MIF expression. Quantitative real-time PCR and Western blot analysis showed high MIF protein and mRNA expression at 7–10 wk and lower levels at 11–12 wk until term. Exposure of villous explants to 3% O2 resulted in increased MIF expression and secretion relative to standard conditions (20% O2). DMOG treatment under 20% O2 increased MIF expression. In situ hybridization and immunohistochemistry showed elevated MIF expression in low oxygen-induced extravillous trophoblast cells. Finally, a significant increase in MIF transcript was observed in placental tissues from high-altitude pregnancies. Hence, three experimental models of placental hypoxia (early gestation, DMOG treatment, and high altitude) converge in stimulating increased MIF, supporting the conclusion that placental-derived MIF is an oxygen-responsive cytokine highly expressed in physiological in vivo and in in vitro low oxygen conditions.

scholarly journals Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1

2020 ◽  
Vol 64 (2) ◽  
Author(s):  
Carla Loreto ◽  
Rosario Caltabiano ◽  
Adriana Carol Eleonora Graziano ◽  
Sergio Castorina ◽  
Claudia Lombardo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Lung Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Macrophage Migration

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

scholarly journals Macrophage migration inhibitory factor exerts pro-proliferative and anti-apoptotic effects via CD74 in murine hepatocellular carcinoma

2020 ◽  
Author(s):  
Theresa Wirtz ◽  
Alena Saal ◽  
Irina Bergmann ◽  
Petra Fischer ◽  
Daniel Heinrichs ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Surrounding Tissue ◽  
Macrophage Migration ◽  
Tumour Burden ◽  
The Impact

Background and Purpose: Macrophage migration inhibitory factor (MIF) is an inflammatory and chemokine-like protein expressed in different diseases as well as solid tumours. Here, CD74 – as the cognate MIF receptor – was identified as an important target of MIF. We analysed the role of MIF and CD74 in the progression of hepatocellular carcinoma (HCC) in vitro and in vivo using an experimental murine HCC model. Experimental Approach: Multilocular HCC was induced using the diethylnitrosamine/carbon tetrachloride (DEN/CCl4) model in hepatocyte-specific Mif knockout (Mif Δhep), CD74-deficient, and control mice. Tumour burden was compared between the genotypes. MIF, CD74 and Ki67 expression were investigated in tumour and surrounding tissue. In vitro, the impact of the MIF/CD74 axis on the proliferative and apoptotic behaviour of hepatoma cells was assessed after stimulation with MIF and anti-CD74 antibodies. Key Results: DEN/CCl4 treatment of Mif Δhep mice resulted in reduced tumour burden and diminished proliferation capacity within the tumour tissue. In vitro, MIF stimulated the proliferation of Hepa 1-6 cells and inhibited therapy-induced cell death as evidenced by TUNEL-staining. Both effects could be reversed using a neutralizing anti-CD74 antibody, and Cd74-/- mice developed fewer tumours associated with decreased proliferation rates. Conclusion and Implications: In this study, we identified a pro-tumorigenic role of MIF during proliferation and therapy-induced apoptosis of HCC cells. Furthermore, our study implicates that these effects are mediated via the MIF cognate receptor CD74. In conclusion, the inhibition of the MIF/CD74 axis could present a promising target with regard to prospective HCC-directed pharmacological therapies.

scholarly journals Macrophage Migration Inhibitory Factor Promotes the Interaction between the Tumor, Macrophages, and T Cells to Regulate the Progression of Chemically Induced Colitis-Associated Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Thalia Pacheco-Fernández ◽  
Imelda Juárez-Avelar ◽  
Oscar Illescas ◽  
Luis I. Terrazas ◽  
Rogelio Hernández-Pando ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Intestinal Epithelium ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Chemical Carcinogenesis ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Initial Development ◽  
The Impact

Colitis-associated colorectal cancer (CRC) development has been shown to be related to chronically enhanced inflammation. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator that favors inflammatory cytokine production and has chemotactic properties for the recruitment of macrophages (Møs) and T cells. Here, we investigated the role of MIF in the inflammatory response and recruitment of immune cells in a murine model of chemical carcinogenesis to establish the impact of MIF on CRC genesis and malignancy. We used BALB/c MIF-knockout (MIF-/-) and wild-type (WT) mice to develop CRC by administering intraperitoneal (i.p.) azoxymethane and dextran sodium sulfate in drinking water. Greater tumor burdens were observed in MIF-/- mice than in WT mice. Tumors from MIF-/- mice were histologically identified to be more aggressive than tumors from WT mice. The localization of MIF suggests that it is also involved in cell differentiation. The relative gene expression of il-17, measured by real-time PCR, was higher in MIF-/- CRC mice, compared to the WT CRC and healthy MIF-/- mice. Importantly, compared to the WT intestinal epithelium, lower percentages of tumor-associated Møs were found in the MIF-/- intestinal epithelium. These results suggest that MIF plays a role in controlling the initial development of CRC by attracting Møs to the tumor, which is a condition that favors the initial antitumor responses.

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