Elsevier

Kidney International

Volume 67, Issue 3, March 2005, Pages 867-874
Kidney International

Hormones – Cytokines – Signalling
EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-γ–dependent mechanism

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EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-γ–dependent mechanism.

Background

Recent studies have shown that fish oil, containing ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) (C20:5 ω 3), and docosahexaenoic acid (DHA) (C22:6 ω 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 ω-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 ω-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 ω-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 μmol/L and 100 μmol/L concentrations effectively decreased lipopolysaccharide (LPS)-induced nuclear factor-kappaB (NF-κB) activation and monocyte chemoattractant protein-1 (MCP-1) expression. EPA and DHA also increased both PPAR-γ mRNA and protein activity (two- to threefold) in HK-2 cells. A dose of 100 μmol/L bisphenol A diglycidyl ether (BADGE) abolished the PPAR-γ activation induced by both EPA and DHA and removed the inhibitory effect of EPA and DHA on LPS-induced NF-κB activation in HK-2 cells. Overexpression of PPAR-γ further inhibited NF-κB 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-κB via a PPAR-γ–dependent pathway in HK-2 cells. These results suggest that PPAR-γ activation by EPA and DHA may be one of the underlying mechanisms for the beneficial effects of fish oil.

Keywords

ω-3 polyunsaturated fatty acids
PPARγ
NF-κ B

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