title: L-Arginine modulates CXC chemokines in the human intestinal epithelial cell line HCT-8 by the NO pathway.
abstract: Arginine has immunomodulating properties in different animal models but its effects in human intestine remain unknown. This study examined whether arginine modulates inflammatory mediators as chemokines and nitric oxide (NO) in the human intestinal epithelial cell line HCT-8 induced by cytokines. Under basal conditions, arginine did not influence iNOS protein expression, NO and chemokine production and mRNA levels (P>0.05 for all). Stimulation with cytokines-induced a significant increase of NO and chemokine production, iNOS and chemokine mRNA level and iNOS protein expression. Under inflammatory conditions, arginine increased 30% NO production (P<0.05) but did not influence iNOS mRNA level or iNOS protein expression. Under stimulated conditions, arginine decreased IL-8 and Mig mRNA level (57% and 39%, for 0.1 vs. 2 mmol/l l-arginine, P<0.05, respectively), and production (respectively, 28 and 23%, both P<0.05). IP-10 and I-TAC mRNA level and production were not significantly influenced by arginine. Under inflammatory conditions, l-arginine as well as a NO donor (sodium nitroprusside (SNP)) increased NO production, which was inversely correlated with IL-8 production (r'=-0.66, P=0.007 for arginine; r'=-0.79, P<0.0001 for SNP). Use of NG-Methyl-l-arginine acetate, a NOS inhibitor which prevents arginine-induced NO production, suppressed the arginine-induced IL-8 inhibition (P<0.05). In HCT-8 cells, arginine enhanced cytokine-induced NO production, reduced IL-8 and Mig production and mRNA level and had no effects on other assessed chemokines. In conclusion, arginine-induced IL-8 inhibition in HCT-8 cells involves NO pathway under inflammatory conditions. These data suggest that arginine-enriched enteral nutrition may have significant influence on inflammatory response in human intestine.
authors.affiliation: Appareil Digestif Environnement Nutrition (ADEN EA 3234), Faculté de Médecine-Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (I.F.R. 23), 22, boulevard Gambetta, 76183 Rouen cedex, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marion
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lemoulan
authors.forename: Gilles
authors.initials: G
authors.lastname: Gargala
authors.forename: Philippe
authors.initials: P
authors.lastname: Ducrotté
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
mesh_terms: D000230:Adenocarcinoma; D001120:Arginine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors; D012333:RNA, Messenger / Q000235:genetics; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019743:Chemokines, CXC; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine