title: Eicosapentaenoic acid regulates IκBα and prevents tubulointerstitial injury in kidney.
abstract: Fish oil containing n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is well known to prevent the progression of IgA nephropathy. However, the mechanism through which fish oil prevents the progression of renal injury remains uncertain. We tried to clarify the effects of EPA on tubulointerstitial injury in the kidney both in vivo and in vitro. We examined the effects of EPA, especially to focus on nuclear factor kappa B (NF-κB), using Thy-1 nephritis models. Also the mechanism of EPA was investigated using small-interfering RNA (siRNA) in lipopolysaccharide (LPS)-stimulated proximal tubular epithelial cells (PTECs). In Thy-1 nephritis models, EPA significantly inhibited tubulointerstitial injury and the infiltration of macrophages into tubulointerstitial lesions except severe glomerular injury at early stage. Compared with control animals, NF-κB activation was significantly augmented in the Thy-1 nephritic kidney. However, treatment with EPA significantly reduced NF-κB activation, down-regulated the expressions of NF-κB-dependent molecules. Also in LPS-stimulated PTECs, LPS augmented NF-κB activation and the expression of NF-κB-dependent molecules. As in the case with the Thy-1 nephritis models, treatment with EPA inhibited them, prevented the degradation of IκBα in LPS-stimulated PTECs. Pre-treatment with siRNA for IκBα abolished the inhibitory effect of EPA on LPS-induced NF-κB activation, suggesting that EPA inhibited NF-κB activation by regulating IκBα. Our results indicate that EPA prevents the early progression of tubulointerstitial injury in Thy-1 nephritis models, and the inhibitory effect of EPA on the expression of inflammatory molecules via the regulation of IκBα in cultured cells may explain this mechanism.
authors.affiliation: Department of Clinical Renal Regeneration, and Division of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takase
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hishikawa
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kamiura
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakakuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawano
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020672:I-kappa B Proteins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D007687:Kidney Tubules, Proximal / Q000166:cytology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D020011:Protective Agents; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D015118:Eicosapentaenoic Acid; D020928:Mitogen-Activated Protein Kinases