title: Agonist of peroxisome proliferator-activated receptor-gamma, rosiglitazone, reduces renal injury and dysfunction in a murine sepsis model.
abstract: BACKGROUND
  Agonists of the peroxisome proliferator-activated receptor-gamma may help to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to determine the protective effects of rosiglitazone on renal injury in a sepsis model and to explore the mechanism.
  
  
  METHODS
  In lipopolysaccharide (LPS)-induced mouse sepsis, we examined the effect of rosiglitazone on LPS-induced overproduction of inflammatory mediators, on the expression of adhesion molecules in renal tubular epithelial cells and on renal function. The mechanism of the protective effect was investigated in vitro using human renal tubular epithelial cells.
  
  
  RESULTS
  Rosiglitazone significantly decreased serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels during sepsis. The levels of blood urea nitrogen and creatinine were significantly lower in mice pre-treated with rosiglitazone than that in LPS-treated mice. Rosiglitazone reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tubular epithelial cells and interstitium of LPS-treated mice. Pre-treatment with rosiglitazone reduced the infiltration of macrophages/monocytes in renal tissue. In cultured tubular epithelial cells, rosiglitazone significantly decreased the expression of ICAM-1 and VCAM-1 induced by TNF-alpha or IL-1beta, inhibited the degradation of inhibitor kappaBalpha (IkappaBalpha) and blocked the activation of the p65 subunit of nuclear factor (NF)-kappaB.
  
  
  CONCLUSIONS
  These results indicate that pre-treatment with rosiglitazone attenuated the production of TNF-alpha and IL-1beta and reduced adhesion molecule expression in renal tubular epithelial cells of LPS-treated mice. Rosiglitazone has an anti-inflammatory effect in renal tubular epithelial cells through the inhibition of NF-kappaB activation.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, 634-18, Keum-Am Dong, Jeonju, 561-712, South Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Sang-Ok
authors.initials: SO
authors.lastname: Moon
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000097:blood; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D000077154:Rosiglitazone; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha