title: Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 attenuates renal injury in unilateral ureteral obstructed mice.
abstract: OBJECTIVE
  There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2.
  
  
  METHODS
  We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed.
  
  
  RESULTS
  Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor β (TGF-β) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-β in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys.
  
  
  CONCLUSIONS
  TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, College of Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Dae Eun
authors.initials: DE
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Ki Ryang
authors.initials: KR
authors.lastname: Na
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Kang Wook
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D005650:Fumarates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000804:Angiotensin II; D005650:Fumarates; D012333:RNA, Messenger; D012083:Renin; D051195:Toll-Like Receptor 2; D000092502:Renin Inhibitors; C493486:Tlr2 protein, mouse; C446481:aliskiren
keywords: Renin-angiotensin system; Toll-like receptor 2; Unilateral ureteral obstruction