Hormones – Cytokines – Signalling
Kidney International (2005) 67, 867–874; doi:10.1111/j.1523-1755.2005.00151.x
EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-
–dependent mechanism
HANG LI, XIONG Z RUAN, STEPHEN H POWIS, RAY FERNANDO, WINT Y MON, DAVID C WHEELER, JOHN F MOORHEAD and ZAC VARGHESE
Centre for Nephrology, Royal Free and University College Medical School, University College London, London, United Kingdom; and Department of Nephrology, Peking Union Medical College Hospital, Beijing, People's Republic of China
Correspondence: Dr Xiong Z. Ruan, Centre for Nephrology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. E-mail:xzruan@rfc.ucl.ac.uk
Received 25 February 2004; Revised 16 August 2004; Accepted 22 September 2004.
Abstract
EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-
–dependent mechanism.
Background
Recent studies have shown that fish oil, containing 
-3 polyunsaturated fatty acids (-3 PUFAs) eicosapentaenoic acid (EPA) (C20:5 3), and docosahexaenoic acid (DHA) (C22:6 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 -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 -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 -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 
mol/L and 100 mol/L concentrations effectively decreased lipopolysaccharide (LPS)-induced nuclear factor-kappaB (NF-
B) activation and monocyte chemoattractant protein-1 (MCP-1) expression. EPA and DHA also increased both PPAR-
mRNA and protein activity (two- to threefold) in HK-2 cells. A dose of 100 mol/L bisphenol A diglycidyl ether (BADGE) abolished the PPAR- activation induced by both EPA and DHA and removed the inhibitory effect of EPA and DHA on LPS-induced NF-B activation in HK-2 cells. Overexpression of PPAR- further inhibited NF-B 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-B via a PPAR-–dependent pathway in HK-2 cells. These results suggest that PPAR- activation by EPA and DHA may be one of the underlying mechanisms for the beneficial effects of fish oil.
Keywords:
-3 polyunsaturated fatty acids, PPAR, NF- B
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