Contrasting effects of steroids and mizoribine on macrophage activation and glomerular lesions in rat thy-1 mesangial proliferative glomerulonephritis

American Journal of Nephrology
Yohei IkezumiMakoto Uchiyama

Abstract

Macrophages with a pro-inflammatory (M1) phenotype mediate renal injury in proliferative forms of glomerulonephritis, while alternatively activated (M2) macrophages are thought to be anti-inflammatory and promote repair. Glucocorticoids, the mainstay therapy for proliferative glomerulonephritis, can induce alternative macrophage activation in vitro, but it is unknown whether this occurs in vivo and if this is required for glucocorticoid responsiveness. In addition, clinical studies have suggested that the ability of mizoribine (MZR) to suppress steroid-resistant proliferative glomerulonephritis may operate via inhibiting pro-inflammatory macrophage activation. This study examined prednisolone (PSL) and/or MZR treatment of rat Thy-1 disease - a model in which macrophages promote mesangial proliferative glomerulonephritis. PSL treatment of Thy-1 nephritis induced an M2-like macrophage phenotype, but failed to modify mesangial hypercellularity and actually exacerbated global glomerulosclerosis. In contrast, MZR treatment reduced hypercellularity and glomerulosclerosis and suppressing both M1 and M2 markers of macrophage activation, with a selective reduction in CD169+ macrophages. Combined PSL/MZR treatment suppressed glomerular l...Continue Reading

Citations

Mar 1, 2013·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Yasunori IwataTakashi Wada
Jul 19, 2011·Clinical & Developmental Immunology·Tadahiro KajiyamaYasuhiko Tomino
Jul 2, 2014·Nature Reviews. Nephrology·Xiao-Ming MengHui Yao Lan
Sep 18, 2015·The American Journal of the Medical Sciences·Jun LiBo Gao
Aug 28, 2015·Kidney International Supplements·David J Nikolic-PatersonHui Yao Lan
Mar 11, 2015·World Journal of Pediatrics : WJP·Hiroshi TanakaTaddatsu Imaizumi
Dec 10, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Yohei IkezumiAkihiko Saitoh
Jul 12, 2013·Bioinformatics and Biology Insights·Jurjen W WestraManuel C Peitsch
Feb 7, 2015·American Journal of Physiology. Renal Physiology·Yoshiki HigashijimaMasaomi Nangaku
Sep 2, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Yohei IkezumiDavid J Nikolic-Paterson
Feb 15, 2013·American Journal of Physiology. Renal Physiology·Yingjie HanDavid J Nikolic-Paterson
May 3, 2015·Physiology·Qi CaoYiping Wang
Jan 30, 2019·Nature Reviews. Nephrology·Patrick Ming-Kuen TangHui-Yao Lan
Aug 17, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shun WuGui-Lian Xu
Sep 12, 2021·Clinical Journal of the American Society of Nephrology : CJASN·Caitlyn VlasschaertMichael J Rauh

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