scholarly journals Macrophage Migration Inhibitory Factor (MIF) Inhibition in a Murine Model of Bleomycin-Induced Pulmonary Fibrosis

2018 ◽  
Vol 19 (12) ◽  
pp. 4105 ◽  
Author(s):  
Sven Günther ◽  
Jennifer Bordenave ◽  
Thông Hua-Huy ◽  
Carole Nicco ◽  
Amélie Cumont ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Migration Inhibitory Factor ◽  
Vascular Remodeling ◽  
Macrophage Migration Inhibitory Factor ◽  
Systolic Pressure ◽  
Acid Methyl Ester ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Collagen Deposition ◽  
Inflammatory Infiltration

Background: Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that significantly contributes to morbidity and mortality. Macrophage migration inhibitory factor (MIF) is a critical factor in vascular remodeling of the pulmonary circulation. Objectives: We tested the effects of two small molecules targeting MIF on bleomycin (BLM)-induced collagen deposition, PH, and vascular remodeling in mouse lungs. Methods: We examined the distribution pattern of MIF, CD74, and CXCR4 in the lungs of patients with IPF-PH and the lungs of BLM-injected mice. Then, treatments were realized with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and N-(3-hydroxy-4-fluorobenzyl)-5 trifluoromethylbenzoxazol-2-thione 31 (20 mg/kg/day per os for 3 weeks) started 24 h after an intratracheal BLM administration. Results: More intense immunoreactivity was noted for MIF, CD74, and CXCR4 in lungs from IPF-PH patients and BLM-injected mice. Furthermore, we found that treatments of BLM-injected mice with ISO-1 or compound 31 attenuated lung collagen deposition and right ventricular systolic pressure increase. Additionally, reduced pulmonary inflammatory infiltration and pulmonary arterial muscularization were observed in the lungs of BLM-injected mice treated with ISO-1 or compound 31. Conclusions: Treatments with ISO-1 or compound 31 attenuates BLM-induced inflammation and fibrosis in lung, and prevents PH development in mice, suggesting that MIF is an important factor for IPF-PH development.

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 Macrophage Migration Inhibitory Factor Promotes Cell Death and Aggravates Neurologic Deficits after Experimental Stroke

2010 ◽  
Vol 31 (4) ◽  
pp. 1093-1106 ◽  
Author(s):  
Ana R Inácio ◽  
Karsten Ruscher ◽  
Lin Leng ◽  
Richard Bucala ◽  
Tomas Deierborg
Keyword(s):  
Cell Death ◽  
Migration Inhibitory Factor ◽  
Cortical Neurons ◽  
Macrophage Migration Inhibitory Factor ◽  
Acid Methyl Ester ◽  
Inhibitory Factor ◽  
Experimental Stroke ◽  
Macrophage Migration ◽  
Neurologic Deficits ◽  
The Brain

Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif−/− mice does not affect interleukin-1 β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.

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.

287: Macrophage Migration Inhibitory Factor and its Receptor CD74 are Upregulated in the Urothelium of Interstitial Cystitis Patients

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-96 ◽  
Author(s):  
Pedro L. Vera ◽  
Kenneth A. lczkowski ◽  
Robert M. Moldwin ◽  
Leslie Kushner ◽  
Katherine L. Meyer-Siegler
Keyword(s):  
Interstitial Cystitis ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration
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