title: Paeoniflorin exerts a nephroprotective effect on concanavalin A-induced damage through inhibition of macrophage infiltration.
abstract: BACKGROUND
  It is well established that macrophage infiltration is involved in concanavalin A (conA)-induced liver injury. However, the role of macrophages in conA-induced renal injury remains unknown. The aims of this study were to investigate macrophage infiltration in conA-induced renal injury and determine whether paeoniflorin (PF) could inhibit macrophage infiltration into the kidney.
  
  
  METHODS
  BALB/C mice were pre-treated with or without PF 2 h (h) before conA injection. At 8 h after con A injection, all the mice were sacrificed; The liver and kidney histology were studied. The renal CD68 expression was detected by immunohistochemical and real-time PCR analysis. The level of expression of C-X-C chemokine receptor type 3 (CXCR3) was analyzed by western blot, immunohistochemical and real-time PCR. The pathophysiological involvement of CXCR3 in macrophage infiltration were investigated using dual-colour immunofluorescence microscopy.
  
  
  RESULTS
  PF administration significantly reduced the elevated serum levels of alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine (Cr) and the severity of liver and renal damage compared with that in the conA-vehicle group. PF administration inhibited the increase in renal IL1β mRNA expression and concentration. Furthermore, immunohistochemical analysis showed that macrophages secreted CXCR3 in the kidneys of the conA-vehicle mice. Immunofluorescence microscopy demonstrated CXCR3 bound tightly to C-X-C motif ligand 11 (CXCL11) in the kidneys of the conA-vehicle mice and showed that PF treatment could suppress CXCR3/CXCL11 over-activation.
  
  
  CONCLUSIONS
  Macrophage infiltration was a notable pathological change in the kidneys of conA-treated mice. PF administration attenuated conA-induced renal damage, at least in part, by inhibiting the over-activated CXCR3/CXCL11 signal axis.
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. liucheng0082010@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. cza0907@163.com.
authors.forename: Zhuoan
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. wangyunman_1978@163.com.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. daixiuqin1989@163.com.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Infectious Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. pzxgrk@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. dongying11@citiz.net.
authors.forename: Dongying
authors.initials: D
authors.lastname: Xue
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D054371:Chemokine CXCL11 / Q000378:metabolism; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D039821:Monoterpenes / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D054367:Receptors, CXCR3 / Q000378:metabolism; D006027:Glycosides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054371:Chemokine CXCL11; D003208:Concanavalin A; D005960:Glucosides; D039821:Monoterpenes; D054367:Receptors, CXCR3; C515203:Cxcl11 protein, mouse; C515188:Cxcr3 protein, mouse; C015423:peoniflorin; D006027:Glycosides