title: Medium-chain fatty acids stimulate interleukin-8 production in Caco-2 cells with different mechanisms from long-chain fatty acids.
abstract: OBJECTIVE
  It has been suggested that dietary fat exacerbates intestinal inflammation. We investigated the effect of fatty acids on interleukin (IL)-8 production in a human intestinal epithelial cell line (Caco-2).
  
  
  METHODS
  The cells were cultured as monolayers on microporous membranes in culture inserts. Oleic acid (OA), capric acid (CA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were applied to the apical compartment of Caco-2 cell monolayers. The concentration of IL-8 in the basolateral medium was measured by using enzyme-linked immunosorbent assay, and the expression of IL-8 mRNA was measured by using competitive reverse transcription--polymerase chain reaction. Protein kinase C inhibitors (GF109203X and calphostin C) and H-7 (a protein kinase inhibitor) were used to study the mechanisms by which IL-8 production is stimulated.
  
  
  RESULTS
  Both OA and CA enhanced IL-8 production (approximately fivefold), whereas DHA and EPA did not. Both OA and CA also enhanced IL-1-induced IL-8 production. The onset of OA-induced IL-8 production was delayed compared with that of CA-induced IL-8 production. Both OA and CA enhanced IL-8 mRNA expression (approximately fivefold) after 6 and 3 h, respectively. The protein kinase inhibitor (H-7) reduced both OA- and CA-induced IL-8 production by 88.0 and 85.9%, respectively. The protein kinase C inhibitors (GF109203X and calphostin C) reduced OA-induced IL-8 production by 29.3 and 54.5%, respectively, but showed no effect on CA-induced IL-8 production.
  
  
  CONCLUSIONS
  These findings suggest that not only OA but also CA stimulates IL-8 production in intestinal epithelial cells, and the mechanisms of action differ between OA and CA.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. saitoh@poh.osaka-med.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: O
authors.initials: O
authors.lastname: Saitoh
authors.forename: K
authors.initials: K
authors.lastname: Tabata
authors.forename: R
authors.initials: R
authors.lastname: Matsuse
authors.forename: K
authors.initials: K
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Sugi
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Kayazawa
authors.forename: T
authors.initials: T
authors.lastname: Teranishi
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: I
authors.initials: I
authors.lastname: Hirata
authors.forename: K
authors.initials: K
authors.lastname: Katsu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D018938:Caco-2 Cells; D003652:Decanoic Acids / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D007211:Indoles; D016209:Interleukin-8; D008301:Maleimides; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; C031071:decanoic acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015118:Eicosapentaenoic Acid; D011493:Protein Kinase C; C058819:calphostin C; C070515:bisindolylmaleimide I