PMID- 15698426
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20220408
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 67
IP  - 3
DP  - 2005 Mar
TI  - EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for 
      a PPAR-gamma-dependent mechanism.
PG  - 867-74
AB  - BACKGROUND: Recent studies have shown that fish oil, containing omega-3 
      polyunsaturated fatty acids (omega-3 PUFAs) eicosapentaenoic acid (EPA) (C20:5 
      omega 3), and docosahexaenoic acid (DHA) (C22:6 omega 3) retard the progression 
      of renal disease, especially in IgA nephropathy (IgAN). Despite increasing 
      knowledge of the beneficial effects of fish oils, little is known about the 
      mechanisms of action of omega-3 PUFAs. It has been reported that activation of 
      peroxisome proliferator-activated receptors (PPARs) inhibits production of 
      proinflammatory cytokines. Both EPA and DHA have been shown to activate PPARs. 
      The aim of this study was to examine if omega-3 PUFAs have anti-inflammatory 
      effects via activation of PPARs in human renal tubular cells. METHODS: An 
      immortalized human proximal tubular cell line [human kidney-2 (HK-2) cells] was 
      used in all experiments. Conditioned media was collected from omega-3 PUFAs- 
      treated cells and subjected to enzyme-linked immunosorbent assay (ELISA). Total 
      cellular RNA was isolated from the above cells for real-time quantitative 
      polymerase chain reaction (PCR). Nuclear Extracts were prepared from the HK-2 
      cells for transcription factor activation assay. RESULTS: Both EPA and DHA at 10 
      micromol/L and 100 micromol/L concentrations effectively decreased 
      lipopolysaccharide (LPS)-induced nuclear factor-kappaB (NF-kappaB) activation and 
      monocyte chemoattractant protein-1 (MCP-1) expression. EPA and DHA also increased 
      both PPAR-gamma mRNA and protein activity (two- to threefold) in HK-2 cells. A 
      dose of 100 micromol/L bisphenol A diglycidyl ether (BADGE) abolished the 
      PPAR-gamma activation induced by both EPA and DHA and removed the inhibitory 
      effect of EPA and DHA on LPS-induced NF-kappaB activation in HK-2 cells. 
      Overexpression of PPAR-gamma further inhibited NF-kappaB activation compared to 
      the control cells in the presence of EPA and DHA. CONCLUSION: Our data 
      demonstrate that both EPA and DHA down-regulate LPS-induced activation of 
      NF-kappaB via a PPAR-gamma-dependent pathway in HK-2 cells. These results suggest 
      that PPAR-gamma activation by EPA and DHA may be one of the underlying mechanisms 
      for the beneficial effects of fish oil.
FAU - Li, Hang
AU  - Li H
AD  - Centre for Nephrology, Royal Free and University College Medical School, 
      University College London, London, United Kingdom.
FAU - Ruan, Xiong Z
AU  - Ruan XZ
FAU - Powis, Stephen H
AU  - Powis SH
FAU - Fernando, Ray
AU  - Fernando R
FAU - Mon, Wint Y
AU  - Mon WY
FAU - Wheeler, David C
AU  - Wheeler DC
FAU - Moorhead, John F
AU  - Moorhead JF
FAU - Varghese, Zac
AU  - Varghese Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - F3XRM1NX4H (2,2-bis(4-glycidyloxyphenyl)propane)
SB  - IM
MH  - Benzhydryl Compounds
MH  - Cells, Cultured
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Eicosapentaenoic Acid/*pharmacology
MH  - Epoxy Compounds/pharmacology
MH  - Humans
MH  - Inflammation/*prevention & control
MH  - Lipopolysaccharides/*pharmacology
MH  - NF-kappa B/metabolism
MH  - PPAR gamma/*physiology
EDAT- 2005/02/09 09:00
MHDA- 2005/07/01 09:00
CRDT- 2005/02/09 09:00
PHST- 2005/02/09 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2005/02/09 09:00 [entrez]
AID - S0085-2538(15)50532-2 [pii]
AID - 10.1111/j.1523-1755.2005.00151.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Mar;67(3):867-74. doi: 10.1111/j.1523-1755.2005.00151.x.