Immunomodulatory activity of a gut microbial metabolite of dietary linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, associated with improved antioxidant/detoxifying defences Paolo Bergamo a, *, Diomira Luongo a , Junki Miyamoto b , Ennio Cocca c , Shigenobu Kishino d , Jun Ogawa d , Soichi Tanabe b , Mauro Rossi a a Institute of Food Sciences, National Research Council of Italy (CNR-ISA), Avellino, Italy b Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan c Institute of Biosciences and Bio-Resources, National Research Council of Italy (CNR-IBBR), Naples, Italy d Division of Applied Life Science, Graduate School of Agriculture, Kyoto University, Kyoto, Japan ARTICLE INFO Article history: Received 15 September 2014 Received in revised form 1 October 2014 Accepted 6 October 2014 Available online ABSTRACT Various hydroxy-, oxo-, and conjugated fatty acids are generated by gut microbes through- out the metabolism of dietary PUFAs. Specifically, 10-Hydroxy-cis-12-(HYA), 10-oxo-cis12- (KetoA) and 10-oxo-cis9,trans11-octadecenoic acid (KetoC) are intermediates free fatty acids (iFFA) produced during the isomerization of dietary linoleic acid to cis9,trans11 (c9,t11) isomer of conjugated linoleic acid (CLA). Herein, immunomodulatory and antioxidant activity of selected iFFA was studied in resting (iDCs), LPS-matured DCs (mDCs) and in murine enterocyte cells (MODE-K). Phenotypic maturation of iDCs was not influenced by iFFA, but the release of pro-inflammatory molecules from mDCs was reduced following HYA pre-treatment. HYA ability to improve antioxidant/detoxifying defenses associated with decreased expression of maturation markers in mDCs and in MODE-K cells.The pro-oxidant activity, via NADPH oxidase activation, was responsible for the pro-inflammatory effect of 10-hydroxy- octadecanoic acid. Presented data suggest that the immunomodulatory ability of HYA is determined, at least in part, by its ability to improve antioxidant/detoxifying defenses. © 2014 Elsevier Ltd. All rights reserved. Keywords: Fatty acids Gut microbes Immunomodulation Antioxidant Conjugated linoleic acid Dendritic cells * Corresponding author. Institute of Food Sciences, National Research Council (CNR-ISA), via Roma 64, 83100 Avellino, Italy.Tel.: +39 0825 299506; fax: +39 0825 299161. E-mail address: p.bergamo@isa.cnr.it (P. Bergamo). Chemical compounds studied in this article: cis9,trans11-C18:2 (Pubmed CID 5280644); Diphenyleneiodonium chloride (Pubmed CID: 2733504); lipopolysaccharide (Pubmed CID 11970143); Methyl-beta-cyclodextrin (Pubmed CID 162771); N-Acetyl-L-cysteine (Pubmed CID: 12035); 2-chloro- 5-nitrobenzanilide or GW9662 (Pubmed CID 644213). Abbreviations: c9,t11-CLA, cis9,trans11-C18:2; CLA, conjugated linoleic acid; DCs, dendritic cells; DPI, diphenyleneiodonium chloride; GST, glutathione S-transferase; GCL, γGlutamyl Cysteine Ligase; HYA, 10-hydroxy-cis-12-octadecenoic acid; HYB, 10-hydroxy- octadecanoic acid; iFFA, intermediates free fatty acids; LPS, lipopolysaccharide; KetoA, 10-oxo -cis12-octadecenoic acid; KetoB, 10-oxo- octadecanoic acid; KetoC, 10-oxo-trans11-octadecenoic acid; MβCD, methyl-beta-cyclodextrin; NAC, N-Acetyl Cysteine; NQO1, NADH quinone oxidoreductase; NAC, N-acetyl cysteine; Nrf2, nuclear factor-E2-related factor-2; PPARγ, peroxisome proliferator-activated receptor gamma. http://dx.doi.org/10.1016/j.jff.2014.10.007 1756-4646/© 2014 Elsevier Ltd. All rights reserved. journal of functional foods 11 (2014) 192–202 Available at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locate/jff