scholarly journals Knockdown of Macrophage Migration Inhibitory Factor Disrupts Adipogenesis in 3T3-L1 Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6037-6042 ◽  
Author(s):  
Daisuke Ikeda ◽  
Shinji Sakaue ◽  
Mitsunori Kamigaki ◽  
Hiroshi Ohira ◽  
Naofumi Itoh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Clonal Expansion ◽  
Cell Number ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Transfected Cells ◽  
Mitotic Clonal Expansion

Obesity is a condition in which adipose tissue mass is expanded. Increases in both adipocyte size and number contribute to enlargement of adipose tissue. The increase in cell number is thought to be caused by proliferation and differentiation of preadipocytes. Macrophage migration inhibitory factor (MIF) is expressed in adipocytes, and intracellular MIF content is increased during adipogenesis. Therefore, we hypothesized that MIF is associated with adipocyte biology during adipogenesis and focused on the influence of MIF on adipogenesis. To examine the effects of MIF on adipocytes, MIF expression in 3T3-L1 preadipocytes was inhibited by RNA interference, and cell differentiation was induced by standard procedures. The triglyceride content of MIF small interfering RNA (siRNA)-transfected 3T3-L1 cells was smaller than that of nonspecific siRNA-transfected cells. In addition, MIF knockdown apparently abrogated increases in adiponectin mRNA levels during differentiation. Gene expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP)α, and C/EBPδ decreased with MIF siRNA transfection, but C/EBPβ expression increased. Cell number and incorporation of 5-bromo-2-deoxyuridine into cells decreased from 1–3 d and from 14–20 h, respectively, after induction of differentiation in MIF siRNA-transfected cells, thus suggesting that MIF siRNA inhibits mitotic clonal expansion. Taken together, these results indicated that MIF regulates differentiation of 3T3-L1 preadipocytes, at least partially, through inhibition of mitotic clonal expansion and/or C/EBPδ expression.

scholarly journals Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0137366 ◽  
Author(s):  
Bong-Sung Kim ◽  
Robert Rongisch ◽  
Stephan Hager ◽  
Gerrit Grieb ◽  
Mahtab Nourbakhsh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

scholarly journals A genetic role for macrophage migration inhibitory factor (MIF) in Epinephelus awoara infected with Vibrio parahaemolyticus

2016 ◽  
Vol 14 (3) ◽  
pp. 184-189
Author(s):  
Xiaojin Xu ◽  
Benhong Sang ◽  
Gang Luo
Keyword(s):  
Migration Inhibitory Factor ◽  
Vibrio Parahaemolyticus ◽  
Macrophage Migration Inhibitory Factor ◽  
Head Kidney ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Tissue Levels ◽  
Tnf Α ◽  
Epinephelus Awoara

Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine in immuno-inflammatory diseases. For the first time, we examined the expression of MIF in Epinephelus awoara ( E. awoara). MIF expressions have been detected in the head kidney, spleen, liver, brain, intestine, gill, heart, stomach, and muscle of E. awoara infected with Vibrio parahaemolyticus. The mRNA levels observed in infected groupers were higher than those in healthy groupers. MIF, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) tissue levels have been measured by ELISA. A significant increase in MIF, TNF-α, and IL-1 tissue levels have been found in the treatment groups compared with those in controls. MIF, TNF-α and IL-1 tissue levels in the spleen, head kidney, intestine, and liver of E. awoara during the challenge trial with V. parahaemolyticus were significantly higher than those in controls. There was evidence of functions of MIF in a positive feedback loop with TNF-α and IL-1 that could perpetuate the inflammatory process in grouper infected with V. parahaemolyticus. In conclusion, these results indicated that MIF was related to pathogen-induced immune response.

scholarly journals Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

2012 ◽  
Vol 71 (4) ◽  
pp. 622-633 ◽  
Author(s):  
Orla M. Finucane ◽  
Clare M. Reynolds ◽  
Fiona C. McGillicuddy ◽  
Helen M. Roche
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Metabolic Diseases ◽  
Inhibitory Factor ◽  
Low Grade ◽  
Macrophage Migration ◽  
Pharmacological Agents

High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

Null mutation in macrophage migration inhibitory factor prevents muscle cell loss and fibrosis in partial bladder outlet obstruction

2006 ◽  
Vol 291 (6) ◽  
pp. F1343-F1353 ◽  
Author(s):  
John A. Taylor ◽  
Qing Zhu ◽  
Brian Irwin ◽  
Yazeed Maghaydah ◽  
John Tsimikas ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Bladder Outlet Obstruction ◽  
Macrophage Migration Inhibitory Factor ◽  
Outlet Obstruction ◽  
Inhibitory Factor ◽  
Detrusor Muscle ◽  
Detrusor Underactivity ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Partial Bladder Outlet Obstruction

Idiopathic detrusor underactivity (DU) and detrusor decompensation which develops following partial bladder outlet obstruction (pBOO) are both associated with smooth muscle degeneration and fibrosis. Macrophage migration inhibitory factor (MIF), an important mediator of bladder inflammation, has been shown to promote fibroblast survival and muscle death in other tissues. We evaluated the hypothesis that MIF has similar actions in the bladder by studying detrusor responses to pBOO or sham surgery in anesthetized female mice rendered null for the mif gene (MIF KO) and in wild-type (WT) controls, all killed 3 wk after surgery. WT mice revealed intense MIF immunoreactivity in urothelial cells which decreased, without change in overall mif mRNA levels. Stereologically sound quantitative morphometric measurements were performed in the middetrusor region of each bladder. MIF KO bladders were normal in appearance, yet were 30–40% heavier, with increased middetrusor collagen and muscle, compared with WT controls. In WT mice, pBOO increased the collagen-to-muscle ratio 1.9-fold and middetrusor collagen 1.8-fold, while nucleated muscle counts were 22% lower. In MIF KO mice, by contrast, pBOO had no significant effect on any of these parameters. In primary bladder muscle cultures, treatment with rMIF protein increased TUNEL staining, raising the proportion of early and late apoptotic cells on flow cytometry. Our studies implicate MIF in the sequence of events leading to detrusor muscle loss and fibrosis in obstruction. They raise the possibility that strategies designed to antagonize MIF synthesis, release, or biological activity could prevent or delay DU and urinary retention.

scholarly journals The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Hofmann ◽  
Josefin Soppert ◽  
Tim Ruhl ◽  
Epameinondas Gousopoulos ◽  
Simona Gerra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Erk Signaling ◽  
Macrophage Migration ◽  
Adipose Derived Stem Cells ◽  
Tissue Samples ◽  
Healing Wounds

Background: Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells characterized by their strong regenerative potential and low oxygen consumption. Macrophage migration inhibitory factor (MIF) is a multifunctional chemokine-like cytokine that is involved in tissue hypoxia. MIF is not only a major immunomodulator but also is highly expressed in adipose tissue such as subcutaneous adipose tissue of chronic non-healing wounds. In the present study, we investigated the effect of hypoxia on MIF in ASCs isolated from healthy versus inflamed adipose tissue.Methods: Human ASCs were harvested from 17 patients (11 healthy adipose tissue samples, six specimens from chronic non-healing wounds). ASCs were treated in a hypoxia chamber at <1% oxygen. ASC viability, MIF secretion as well as expression levels of MIF, its receptor CD74, hypoxia-inducible transcription factor-1α (HIF-1α) and activation of the AKT and ERK signaling pathways were analyzed. The effect of recombinant MIF on the viability of ASCs was determined. Finally, the effect of MIF on the viability and production capacity of ASCs to produce the inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1β was determined upon treatment with recombinant MIF and/or a blocking MIF antibody.Results: Hypoxic treatment inhibited proliferation of ASCs derived from healthy or chronic non-healing wounds. ASCs from healthy adipose tissue samples were characterized by a low degree of MIF secretion during hypoxic challenge. In contrast, in ASCs from adipose tissue samples of chronic non-healing wounds, secretion and expression of MIF and CD74 expression were significantly elevated under hypoxia. This was accompanied by enhanced ERK signaling, while AKT signaling was not altered. Recombinant MIF did stimulate HIF-1α expression under hypoxia as well as AKT and ERK phosphorylation, while no effect on ASC viability was observed. Recombinant MIF significantly reduced the secretion of IL-1β under hypoxia and normoxia, and neutralizing MIF-antibodies diminished TNF-α and IL-1β release in hypoxic ASCs.Conclusions: Collectively, MIF did not affect the viability of ASCs from neither healthy donor site nor chronic wounds. Our results, however, suggest that MIF has an impact on the wound environment by modulating inflammatory factors such as IL-1β.

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

2003 ◽  
Vol 285 (6) ◽  
pp. H2500-H2509 ◽  
Author(s):  
Leslie B. Garner ◽  
Monte S. Willis ◽  
Deborah L. Carlson ◽  
J. Michael DiMaio ◽  
Michael D. White ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Cardiac Dysfunction ◽  
Macrophage Migration Inhibitory Factor ◽  
Left Ventricular ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Western Blots ◽  
Endotoxin Challenge ◽  
Lps Challenge

Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24–48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases.

scholarly journals Tissue-specific regulation of inflammation by macrophage migration inhibitory factor and glucocorticoids in fructose-fed Wistar rats

2013 ◽  
Vol 110 (3) ◽  
pp. 456-465 ◽  
Author(s):  
Nataša Veličković ◽  
Ana Djordjevic ◽  
Ana Vasiljević ◽  
Biljana Bursać ◽  
Danijela Vojnović Milutinović ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Metabolic Inflammation ◽  
High Fructose Diet ◽  
High Fructose ◽  
Tnf Α

High fructose consumption is commonly associated with insulin resistance, disturbed glucose homeostasis and low-grade inflammation. Increased glucocorticoid production within adipose tissue has been implicated in the pathogenesis of fructose-induced metabolic syndrome. Immunosuppressive actions of glucocorticoids can be counter-regulated by macrophage migration inhibitory factor (MIF), which is recognised as a key molecule in metabolic inflammation. In the present study, we hypothesised that coordinated action of glucocorticoids and MIF can mediate the effects of a high-fructose diet on adipose tissue and liver inflammation. We examined the effects of long-term consumption of a 10 % fructose solution on corticosterone (CORT) and MIF levels in rat blood plasma, liver and adipose tissue, as well as MIF and TNF-α mRNA expression and NF-κB activation in the same tissues. The high-fructose diet led to an increase in both CORT and MIF in the adipose tissue, and a highly significant positive correlation between their levels was observed. The attenuated NF-κB activation and unaltered TNF-α mRNA expression noticed in the adipose tissue could be interpreted as an outcome of the opposing actions of CORT and MIF. In contrast to adipose tissue, inflammation in the liver was characterised by NF-κB activation, an increased TNF-α mRNA level and unchanged levels of MIF protein, MIF mRNA and CORT. Overall, these findings suggest that a high-fructose diet differently affects the levels of glucocorticoids and MIF in the adipose tissue and liver, implicating that fructose over-consumption has tissue-specific effects on regulation of metabolic inflammation.

scholarly journals Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

2012 ◽  
Vol 20 (1) ◽  
pp. 137-149 ◽  
Author(s):  
Thomas Tawadros ◽  
Florian Alonso ◽  
Patrice Jichlinski ◽  
Noel Clarke ◽  
Thierry Calandra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Tumour Progression ◽  
Serum Levels ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Mrna Levels ◽  
Lncap Cells

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PCa) cells is closely related to tumour progression and hormone resistance. The mechanisms by which NE cells influence PCa growth and progression are not fully understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in oncogenic processes, and MIF serum levels correlate with aggressiveness of PCa. Here, we investigated the regulation and the functional consequences of MIF expression during NE transdifferentiation of PCa cells. NE differentiation (NED) of LNCaP cells, initiated either by increasing intracellular levels of cAMP or by culturing cells in an androgen-depleted medium, was associated with markedly increased MIF release. Yet, intracellular MIF protein and mRNA levels andMIFgene promoter activity decreased during NED of LNCaP cells, suggesting that NED favours MIF release despite decreasing MIF synthesis. Adenoviral-mediated forced MIF expression in NE-differentiated LNCaP cells increased cell proliferation without affecting the expression of NE markers. Addition of exogenous recombinant MIF to LNCaP and PC-3 cells stimulated the AKT and ERK1/2 signalling pathways, the expression of genes involved in PCa, as well as proliferation and resistance to paclitaxel and thapsigargin-induced apoptosis. Altogether, these data provide evidence that increased MIF release during NED in PCa may facilitate cancer progression or recurrence, especially following androgen deprivation. Thus, MIF could represent an attractive target for PCa therapy.

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