PMID- 23887394
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20210108
IS  - 1660-2129 (Electronic)
IS  - 1660-2129 (Linking)
VI  - 123
IP  - 1-2
DP  - 2013
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) modulates lipopolysaccharide-induced 
      chemokine expression by blocking nuclear factor-kappaB activation via peroxisome 
      proliferator activated receptor-gamma-independent mechanism in renal tubular 
      epithelial cells.
PG  - 1-10
LID - 10.1159/000353232 [doi]
AB  - BACKGROUND/AIMS: Inflammation is an unavoidable milieu for renal tubular cells 
      during the development of renal tubulointerstitial fibrosis. It has been 
      demonstrated that chemokines including monocyte chemoattractant protein-1 (MCP-1) 
      and IL-8 are related to tubulointerstitial lesions. 15d-PGJ2 may modulate renal 
      tubulointerstitial fibrosis progression via anti-inflammatory effects. However, 
      no information is known about the effects of 15d-PGJ2 on chemokine expression in 
      human proximal renal tubular cells (HPTECs) under inflammation. METHODS: In the 
      present study, HPTECs (HK-2 cells) were stimulated with lipopolysaccharide (LPS) 
      only, or preincubated with 15d-PGJ2. IL-8 and MCP-1 expressions were determined 
      by real-time PCR and ELISA. Nuclear factor-kappaB (NF-kappaB) location was detected by 
      immunofluorescence analysis. The p-IKK, p-IkappaBalpha and p65/p50 were analyzed by 
      immunoblotting. To investigate the mechanism of inhibitory effects of 15d-PGJ2, 
      the PPAR-gamma gene was effectively silenced in HK-2 cells using specific siRNA. 
      RESULTS: The results showed that application of LPS significantly increased IL-8 
      and MCP-1 production. Phosphorylation of IkappaBalpha, IKK and nucleus translocation of 
      NF-kappaB significantly increased in LPS-stimulated HK-2 cells. 15d-PGJ2 
      downregulated LPS-induced IL-8 and MCP-1 production. Interestingly, in 
      PPAR-gamma-deficient HK-2 cells, 15d-PGJ2 was still capable of inhibiting chemokines 
      expression and attenuating phosphorylation of IkappaBalpha and nucleus translocation of 
      NF-kappaB. CONCLUSION: Collectively, these results suggest that 15d-PGJ2 exerts 
      anti-inflammatory actions on HK-2 cells by attenuating chemokines expression. 
      15d-PGJ2 inhibits chemokines expression via a PPAR-gamma-independent way, which is 
      related to block NF-kappaB pathway. Since NF-kappaB is an important regulator of the 
      response of HPTECs to injury, PPAR-gamma agonists may represent a key pharmacological 
      target for ameliorating inflammation-associated tubulointerstitial fibrosis.
CI  - (c) 2013 S. Karger AG, Basel.
FAU - Lu, Ying
AU  - Lu Y
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, 
      Shanghai, PR China.
FAU - Zhou, Qiao
AU  - Zhou Q
FAU - Zhong, Fang
AU  - Zhong F
FAU - Guo, Shanmai
AU  - Guo S
FAU - Hao, Xu
AU  - Hao X
FAU - Li, Cong
AU  - Li C
FAU - Wang, Weiming
AU  - Wang W
FAU - Chen, Nan
AU  - Chen N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130724
PL  - Switzerland
TA  - Nephron Exp Nephrol
JT  - Nephron. Experimental nephrology
JID - 101159770
RN  - 0 (15-deoxy-delta(12,14)-prostaglandin J2)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (PPAR gamma)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokines/genetics/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Immunoblotting
MH  - Interleukin-8/genetics/metabolism
MH  - Kidney Tubules, Proximal/cytology
MH  - Lipopolysaccharides/*pharmacology
MH  - Microscopy, Fluorescence
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - PPAR gamma/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Prostaglandin D2/*analogs & derivatives/pharmacology
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
EDAT- 2013/07/28 06:00
MHDA- 2014/03/04 06:00
CRDT- 2013/07/27 06:00
PHST- 2012/11/20 00:00 [received]
PHST- 2013/07/25 00:00 [accepted]
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
AID - 000353232 [pii]
AID - 10.1159/000353232 [doi]
PST - ppublish
SO  - Nephron Exp Nephrol. 2013;123(1-2):1-10. doi: 10.1159/000353232. Epub 2013 Jul 
      24.