scholarly journals Implantation of Dedifferentiated Fat Cells Ameliorated ANCA Glomerulonephritis by Immunosuppression and Increases in TSG-6

2021 ◽  
Author(s):  
Kei Utsunomiya ◽  
Takashi Maruyama ◽  
Satoshi Shimizu ◽  
Taro Matsumoto ◽  
Morito Endo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Therapy ◽  
Tumor Necrosis ◽  
Protein A ◽  
Survival Rates ◽  
Interleukin 10 ◽  
M2 Macrophages ◽  
Crescent Formation ◽  
Dfat Cells ◽  
Necrosis Factor

Abstract We examined the effects of implantation of dedifferentiated fat (DFAT) cells on renal function, proteinuria and glomerulonephritis in SCG mice as a preclinical study of DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis and investigated mechanisms underlying the immunosuppressive effects of the implantation of DFAT cells. After their intravenous infusion, almost all DFAT cells were trapped in the lung and not delivered into the kidney. Implantation of DFAT cells in SCG mice suppressed glomerular crescent formation, decreased urinary protein excretions, and increased expression of tumor necrosis factor-stimulated gene-6 (TSG-6) mRNA, protein and immunostaining in kidney from these mice. Implantation of DFAT cells increased the expression of microRNA 23b-3p in plasma, kidney and lung in SCG mice and decreased the expression of CD44 mRNA and increased the expression of prostaglandin E2 and interleukin-10 mRNAs in kidney from these mice. Implantation of DFAT cells increased expression of TSG-6 protein and decreased expression of tumor necrosis factor-a protein in kidney from SCG mice. Further, implantation of DFAT cells increased the expression of C-C motif chemokine ligand 17 protein, a chemokine for M2 macrophages, and decreased the expression of MCP-1 protein, a chemokine for M1 macrophages, in kidney from SCG mice. Survival rates were higher in SCG mice with implantation of DFAT cells than in SCG mice without implantation. These results indicate that implantation of DFAT cells suppressed renal injury including glomerular crescent formation in kidney from SCG mice while increasing the expression of TSG-6 without delivery of DFAT cells directly into kidney. Mechanisms underlying the effects of improvement of ANCA glomerulonephritis are associated with immunosuppressive effects by TSG-6 and the transition of M1 to M2 macrophages. These findings suggest that implantation of DFAT cells may become a cell therapy for ANCA glomerulonephritis.

scholarly journals Genetic Variations in Tumor Necrosis Factor Alpha, Interleukin-10 Genes, and Migraine Susceptibility

Pain Medicine ◽  
2011 ◽  
Vol 12 (10) ◽  
pp. 1464-1469 ◽  
Author(s):  
Omer Ates ◽  
Semiha Kurt ◽  
Julide Altinisik ◽  
Hatice Karaer ◽  
Saime Sezer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Genetic Variations ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Targeted Deletion of Class A Macrophage Scavenger Receptor Increases the Risk of Cardiac Rupture After Experimental Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1904-1911 ◽  
Author(s):  
Kenichi Tsujita ◽  
Koichi Kaikita ◽  
Takanori Hayasaki ◽  
Tsuyoshi Honda ◽  
Hironori Kobayashi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Experimental Myocardial Infarction ◽  
Cardiac Rupture ◽  
Infarcted Myocardium ◽  
Factor Α ◽  
Necrosis Factor

Background— Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A–deficient (SR-A −/− ) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction. Methods and Results— Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A −/− and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A −/− mice than in WT mice ( P =0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A −/− mice and 12% (6 of 51 mice) in WT mice ( P =0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A −/− mice compared with WT mice. Real-time reverse transcription–polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A −/− mice compared with WT mice. Furthermore, SR-A −/− mice showed augmented expression of tumor necrosis factor-α and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-α and decreased interleukin-10 expression in activated SR-A −/− macrophages. Conclusions— The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-α and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.

Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-α

1995 ◽  
Vol 25 (10) ◽  
pp. 2888-2893 ◽  
Author(s):  
Johannes Barsig ◽  
Sabine Küsters ◽  
Kathrin Vogt ◽  
Hans-Dieter Volk ◽  
Gisa Tiegs ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor Receptor p55-Deficient Mice Respond to Acute Yersinia enterocolitica Infection with Less Apoptosis and More Effective Host Resistance

2000 ◽  
Vol 68 (3) ◽  
pp. 1243-1251 ◽  
Author(s):  
Yi-Xue Zhao ◽  
Ginette Lajoie ◽  
Hongwei Zhang ◽  
Basil Chiu ◽  
Ursula Payne ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Yersinia Enterocolitica ◽  
Acute Phase ◽  
Host Defense ◽  
Bacterial Infections ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Interleukin 10 ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55−/−). Unexpectedly, TNFRp55−/− mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4+-T-cell population of splenocytes, whereas TNFRp55−/− mice were spared these changes. The splenocytes from TNFRp55−/− mice also maintained a robust gamma interferon IFN-γ response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55−/− mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.

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