scholarly journals Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 175-182 ◽  
Author(s):  
F Arcuri ◽  
M Cintorino ◽  
A Carducci ◽  
S Papa ◽  
M G Riparbelli ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
K562 Cells ◽  
Cytolytic Activity ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner ◽  
Unk Cells

The human uterine mucosa of early pregnancy is largely populated by CD56brightnatural killer (NK) cells (uterine (u) NK cells). The specific functions of these cells are still unknown, but their interaction and response to foetal trophoblasts are thought to be important for the establishment of a successful pregnancy. The study reported herein shows that uNK cells respond to, and produce, macrophage migration inhibitory factor (MIF), a cytokine highly expressed in the human placenta and in the cyclic and pregnant endometrium. Recombinant human MIF reduced in a dose-dependent manner the cytolytic activity of purified uNK cells against K562 cells. RT-PCR, Western blot analysis and ELISA demonstrated the synthesis and secretion of the cytokine by uNK cells. Double immunofluorescence staining showed the presence of MIF in uterine CD56 + cells. Finally, neutralization of the endogenous cytokine by a polyclonal antibody resulted in a sharp increase in the cytolytic activity of uNK cells. These findings indicate the existence of a previously unrevealed paracrine and autocrine action of MIF on uNK cells and support its contribution to the immune privilege at the maternal–foetal interface.

scholarly journals Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis

2019 ◽  
Vol 20 (15) ◽  
pp. 3753 ◽  
Author(s):  
Wirtz ◽  
Fischer ◽  
Backhaus ◽  
Bergmann ◽  
Brandt ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Migration Inhibitory Factor ◽  
Promoter Region ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner ◽  
Microsatellite Repeats

Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) - rs755622 and rs5844572 - exhibit prognostic relevance in inflammatory diseases. The aim of this study was to investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5–8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, ≥7 microsatellite repeats were associated with lower fibrosis stages (<F2) (p = 0.04). Comparable tendencies were observed in the second independent cohort, where fibrosis was assessed using transient elastography. However, once cirrhosis had been established, the C/C genotype and higher microsatellite repeats correlated with impaired liver function and a higher prevalence of hepatocellular carcinoma. Our study demonstrates that specific MIF polymorphisms are associated with disease severity and complications of HCV-induced fibrosis in a stage- and context-dependent manner.

scholarly journals Redox-dependent Structure and Dynamics of Macrophage Migration Inhibitory Factor Reveal Sites of Latent Allostery

2021 ◽  
Author(s):  
Erin Skeens ◽  
Meagan M Gadzuk-Shea ◽  
Dilip Shah ◽  
Vineet Bhandari ◽  
Devin K Schweppe ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Mutational Analysis ◽  
Redox Conditions ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner ◽  
Structure Based Drug Design ◽  
Cellular Environment ◽  
Wide Range

Macrophage migration inhibitory factor (MIF) is a multifunctional immunoregulatory protein that is a key player in the innate immune response. Given its overexpression at sites of inflammation in a wide range of diseases marked by increasingly oxidative cellular environment, a comprehensive structural understanding of how cellular redox conditions may impact the structure and function of MIF is necessary. We used solution NMR spectroscopy and mass spectrometry to investigate structural and dynamic signatures of MIF under varied solution redox conditions. Our results indicate that the MIF structure is modified and becomes increasingly dynamic in an oxidative environment, which may be a means to alter the MIF functional response in a redox-dependent manner. We identified latent allosteric sites within MIF that are redox-sensitive and mutational analysis reveals that loss of redox-responsive residues attenuates activation of the coreceptor CD74. Leveraging sites of redox-sensitivity therefore reveals an avenue to modulate MIF function in its disease state via structure-based drug design.

scholarly journals Glioma-derived macrophage migration inhibitory factor (MIF) promotes mast cell recruitment in a STAT5-dependent manner

2013 ◽  
Vol 8 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Jelena Põlajeva ◽  
Tobias Bergström ◽  
Per-Henrik Edqvist ◽  
Anders Lundequist ◽  
Anna Sjösten ◽  
...  
Keyword(s):  
Mast Cell ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner ◽  
Cell Recruitment

scholarly journals Macrophage Migration Inhibitory Factor Activates Hypoxia-Inducible Factor in a p53-Dependent Manner

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2215 ◽  
Author(s):  
Seiko Oda ◽  
Tomoyuki Oda ◽  
Kenichiro Nishi ◽  
Satoshi Takabuchi ◽  
Takuhiko Wakamatsu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner

scholarly journals Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257375
Author(s):  
Shin Heon Lee ◽  
Hyung Joon Kwon ◽  
Saewhan Park ◽  
Chan Il Kim ◽  
Haseo Ryu ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Signaling Pathway ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Dependent Manner ◽  
Dual Inhibitor ◽  
Pathway Activation

Radiation therapy is among the most essential treatment methods for glioblastoma multiforme (GBM). Radio-resistance and cancer stem cell properties can cause therapeutic resistance, cancer heterogeneity, and poor prognoses in association with GBM. Furthermore, the GBM subtype transition from proneural to the most malignant mesenchymal subtype after radiation therapy also accounts for high resistance to conventional treatments. Here, we demonstrate that the inhibition of macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) by 4-iodo-6-phenylpyrimidine (4-IPP), a dual inhibitor targeting MIF and DDT, downregulates stemness phenotype, intracellular signaling cascades, mesenchymal trans-differentiation, and induces apoptosis in proneural glioma stem cells (GSCs). In an analysis of The Cancer Genome Atlas, high MIF and DDT expression were associated with poor prognosis. GSC growth was effectively inhibited by 4-IPP in a time- and dose-dependent manner, and 4-IPP combined with radiation therapy led to significantly reduced proliferation compared with radiation therapy alone. The expression of stemness factors, such as Olig2 and SOX2, and the expression of pAKT, indicating PI3K signaling pathway activation, were decreased in association with both 4-IPP monotherapy and combination treatment. The expression of mesenchymal markers, TGM2 and NF-κB, and expression of pERK (indicating MAPK signaling pathway activation) increased in association with radiation therapy alone but not with 4-IPP monotherapy and combination therapy. In addition, the combination of 4-IPP and radiation therapy significantly induced apoptosis compared to the monotherapy of 4-IPP or radiation. In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.

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