PMID- 21734368
OWN - NLM
STAT- MEDLINE
DCOM- 20120118
LR  - 20181201
IS  - 1421-9670 (Electronic)
IS  - 0250-8095 (Linking)
VI  - 34
IP  - 2
DP  - 2011
TI  - Inhibitory effects of rosiglitazone on lipopolysaccharide-induced inflammation in 
      a murine model and HK-2 cells.
PG  - 152-62
LID - 10.1159/000329120 [doi]
AB  - BACKGROUND: Inflammation may play an important role in the pathogenesis of kidney 
      disease. Agonists of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), 
      such as rosiglitazone, have been recently demonstrated to regulate inflammation 
      by modulating the production of inflammatory mediators. The purpose of this study 
      was to examine the effects of rosiglitazone on lipopolysaccharide (LPS)-induced 
      kidney inflammation and to explore the mechanism of its renoprotection. METHODS: 
      Mice were treated with LPS with or without pretreatment with rosiglitazone. Blood 
      urea nitrogen (BUN), creatinine levels, the urinary albumin-to-creatinine ratio, 
      macrophage infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, 
      PPAR-gamma expression, and NF-kappaB and PPAR-gamma activity were investigated. HK-2 cells 
      were maintained under defined in vitro conditions, treated with either 
      rosiglitazone and/or the PPAR-gamma antagonist GW9662, and then stimulated with LPS. 
      MCP-1, IL-8, IL-6, NF-kappaB activity and PPAR-gamma expression were investigated. 
      RESULTS: Compared to the LPS only group, pretreatment with rosiglitazone in vivo 
      significantly attenuated the BUN levels macrophage infiltration, MCP-1 
      overexpression and NF-kappaB activity (p < 0.05). Rosiglitazone also restored PPAR-gamma 
      expression and protein activity, which were reduced significantly in the LPS only 
      group (p < 0.05). Furthermore, in the LPS-stimulated HK-2 cells, rosiglitazone 
      downregulated MCP-1, IL-8 and IL-6 expression as well as NF-kappaB activation and 
      increased PPAR-gamma expression (p < 0.05). These effects were diminished by GW9662. 
      CONCLUSION: These results showed that pretreatment with rosiglitazone could 
      attenuate kidney inflammation through the activation of PPAR-gamma, suppression of 
      MCP-1 overproduction and NF-kappaB activation. Rosiglitazone had a protective effect 
      via a PPAR-gamma-dependent pathway in LPS-treated HK-2 cells.
CI  - Copyright (c) 2011 S. Karger AG, Basel.
FAU - Wang, W M
AU  - Wang WM
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, PR 
      China.
FAU - Chen, H
AU  - Chen H
FAU - Zhong, F
AU  - Zhong F
FAU - Lu, Y
AU  - Lu Y
FAU - Han, L
AU  - Han L
FAU - Chen, N
AU  - Chen N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110704
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Anilides/pharmacology
MH  - Animals
MH  - Blood Urea Nitrogen
MH  - Chemokine CCL2/biosynthesis
MH  - Creatinine/blood
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Inflammation
MH  - Interleukin-6/biosynthesis
MH  - Interleukin-8/biosynthesis
MH  - Lipopolysaccharides/*metabolism
MH  - Male
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - PPAR gamma/metabolism
MH  - Reactive Oxygen Species
MH  - Rosiglitazone
MH  - Thiazolidinediones/*pharmacology
MH  - Time Factors
EDAT- 2011/07/08 06:00
MHDA- 2012/01/19 06:00
CRDT- 2011/07/08 06:00
PHST- 2010/12/28 00:00 [received]
PHST- 2011/05/04 00:00 [accepted]
PHST- 2011/07/08 06:00 [entrez]
PHST- 2011/07/08 06:00 [pubmed]
PHST- 2012/01/19 06:00 [medline]
AID - 000329120 [pii]
AID - 10.1159/000329120 [doi]
PST - ppublish
SO  - Am J Nephrol. 2011;34(2):152-62. doi: 10.1159/000329120. Epub 2011 Jul 4.