Inhibition of Macrophage Migration Inhibitory Factor (MIF) as a Therapeutic Target in Bleomycin-InducedPulmonary Fibrosis Rats

2021 ◽  
Author(s):  
Yifeng Luo ◽  
Hui Yi ◽  
Xinyan Huang ◽  
Gengpeng Lin ◽  
Yukun Kuang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Transforming Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Matrix Deposition ◽  
Tgf Β1

Macrophage migration inhibitory factor (MIF) inhibition can attenuates pulmonary fibrosis, but the antifibrotic mechanism is unclear. Here we investigated antifibrotic effect of MIF knockdown in Bleomycin (BLM)-induced pulmonary fibrosis rats. The result showed that MIF inhibition attenuated lung injury and extracellular matrix deposition, significantly reduced the levels of cytokines including Transforming growth factor-β1(TGF-β1), TNF-α, IL-17, hydroxyproline (hyp), fibroblast growth factor 23 (FGF23) and secreted phosphoprotein 1 (Spp1), and inhibited the expression of CD68, F4/80 and α-smooth muscle actin(α-SMA) protein. MIF inhibition is associated with reduction of pro-inflammatory mediators and macrophage infiltration in lungs. In addition, MIF knockdown in the Day14 group was significantly better than MIF knockdown in Day1 group in terms of the above cytokines. MIF knockdown in Day14 group showed a better trend than MIF knockdown in Day1 group in inhibition of hyp and α-SMA formation. Furthermore, MIF inhibition induced down-regulated the FGF23, Spp1, Itga10, Lama1, Thbs2, Serpinb5 mRNA level and p-Smad2/3 protein level. MIF knockdown may inhibit fibrosis through the TGF-β1/Smads signaling pathway. What' more, MIF inhibition protects also against vascular remodeling via Thbs2 and Serpinb5 signaling. In summary, our study showed that knockdown of MIF can significantly inhibit lung inflammation and fibrosis in BLM-induced pulmonary fibrosis rats. The future development of inhibitors targeting MIF may contribute to the treatment of pulmonary fibrosis.

scholarly journals Macrophage Migration Inhibitory Factor Regulates Joint Capsule Fibrosis by Promoting TGF-β1 Production in Fibroblasts

2020 ◽  
Author(s):  
Yuxin Zhang ◽  
Shenji Lu ◽  
Kexin Wang ◽  
Shuai Fan ◽  
Lili Xu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Transforming Growth Factor ◽  
Membrane Surface ◽  
Joint Capsule ◽  
Inhibitory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Specific Cell ◽  
Macrophage Migration ◽  
Tgf Β1

Abstract Background: Joint capsule fibrosis caused by excessive inflammation results in post-traumatic joint contracture (PTJC). Transforming growth factor (TGF)-β1 plays a key role in PTJC by regulating fibroblast functions, however, cytokine-induced TGF-β1 expression in specific cell types remains poorly characterized. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology. Results: In this study, we investigated whether MIF can facilitate TGF-β1 production from fibroblasts and regulate joint capsule fibrosis following PTJC. Our data demonstrated that MIF and TGF-β1 significantly increased in fibroblasts of injured rat posterior joint capsules. Treatment the lesion sites with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP) reduced TGF-β1 production and relieved joint capsule inflammation and fibrosis. In vitro, MIF facilitated TGF-β1 expression in primary joint capsule fibroblasts by activating mitogen-activated protein kinase (MAPK) (P38, ERK) signaling through coupling with membrane surface receptor CD74, which in turn affected fibroblast functions and promoted MIF production. Conclusion: Our results reveal a novel function of trauma-induced MIF in the occurrence and development of joint capsule fibrosis. Further investigation of the underlying mechanism may provide potential therapeutic targets for PTJC.

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients

2016 ◽  
Vol 42 (5) ◽  
pp. 263-266 ◽  
Author(s):  
Carmela Olivieri ◽  
Elena Bargagli ◽  
Simona Inghilleri ◽  
Ilaria Campo ◽  
Marcella Cintorino ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Tissue ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration

scholarly journals Impact of a Low-Glucose Peritoneal Dialysis Regimen on Fibrosis and Inflammation Biomarkers

2015 ◽  
Vol 35 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Susan Yung ◽  
Sing Leung Lui ◽  
Chris K.F. Ng ◽  
Andrew Yim ◽  
Maggie K.M. Ma ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Adhesion Molecule ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Membrane Integrity ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Vascular Endothelial ◽  
Low Glucose

BackgroundThe impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated.MethodsIn a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, solubleintracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF).ResultsAt the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF.ConclusionChanges in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

Age and sex-specific differences in interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor levels in the tears of healthy subjects

2021 ◽  
pp. 112067212110640
Author(s):  
Dominika Mravec Bencúrová ◽  
Šárka Mandíková ◽  
Pavlína Daňková
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Macrophage Migration ◽  
Vascular Endothelial ◽  
Biological Factors ◽  
Endothelial Growth Factor

Objective To investigate the physiological profile of pro-inflammatory and anti-inflammatory cytokines in tears produced by epithelial cells under the effect of endogenous and exogenous biological factors. Knowing the physiological cytokine profile in tears with its biological characteristics including sex- and age-specific effects is fundamental when tears are analyzed for diagnostic or prognostic purposes in eye diseases. Methods Tear samples were collected from right eye of 45 healthy volunteers (24 males, 21 females) by 5 μl microcapillary tube. Cytokines interleukin 1β, interleukin 10, interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor were quantified by multiplex Bio-Plex system. Results The production of macrophage migration inhibitory factor cytokine by epithelial cells on the ocular surface is higher in males compared to females ( p = 0.05); actually, most of female tear samples present with undetectable macrophage migration inhibitory factor levels. Our results show the negative correlations between the age and concentrations of interleukin 4 ( p < 0.01) and interferon gamma ( p < 0.01) in tears, respectively, and positive associations of vascular endothelial growth factor levels with the age above 45 years ( p < 0.05). Conclusions Data in this study indicate that age and sex may affect the physiological levels of cytokines in tears. Consequently, the impacts of biological factors need to be recognized and taken into consideration before the levels of cytokines in patients’ tears are analyzed for medical reasons. Concentrations of interleukin 1β and interleukin 10 cytokines, however, are very low in healthy tears and do not seem to be influenced by studied biological factors; therefore, they meet the requirements for analytes suitable for medical diagnostic and prognostic purposes.

scholarly journals Inhibition of Macrophage Migration Inhibitory Factor Protects against Inflammation and Matrix Deposition in Kidney Tissues after Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Hong Lu ◽  
Yongyu Bai ◽  
Lianfeng Wu ◽  
Weilong Hong ◽  
Yong Liang ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Related Factors ◽  
Matrix Deposition

Background. Macrophage migration inhibitory factor (MIF) is an important immunoregulatory cytokine involved in inflammation, which may be one important reason resulting in matrix deposition in renal tissues after injury. However, the underlying mechanisms have not yet been elucidated.Methods and Results. We uncovered a crucial role of MIF in inflammation and collagen depositionin vivoandin vitro. In rats, ureteral obstruction induced tubular injury, matrix accumulation, and inflammatory cell infiltration. Additionally, enhanced MIF levels in the obstructed kidneys were closely related to the increasing numbers of CD68-positive macrophages. These obstruction-induced injuries can be relieved by recanalization, consequently resulting in downregulated expression of MIF and its receptor CD74. Similarly, ischemia reperfusion induced renal injury, and it was accompanied by elevated MIF levels and macrophages infiltration. In cultured tubular epithelial cells (TECs), aristolochic acid (AA) promoted matrix production and increased MIF expression, as well as the release of macrophage-related factors. Inhibition of MIF with an antagonist ISO-1 resulted in the abolishment of these genotypes in AA-treated TECs.Conclusion. MIF plays an important role in macrophage-related inflammation and matrix deposition in kidney tissues following injury. MIF as a specific inhibitor may have therapeutic potential for patients with inflammatory and fibrotic kidney diseases.

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