Long-chain polyunsaturated fatty acids attenuate the IL-1β-induced proinflammatory response in human fetal intestinal epithelial cells

Pediatr Res. 2015 Dec;78(6):626-33. doi: 10.1038/pr.2015.154. Epub 2015 Aug 13.

Abstract

Background: Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture.

Methods: Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate with NEC (NEC-IEC). Intestinal cell lines Caco2 and NCM460 in culture were used as models for mature IEC. IEC in culture were pretreated with 100 µmol/l palmitic acid (PAL), DHA, EPA, ARA, or ARA+DHA for 48 h and then stimulated with proinflammatory IL-1β.

Results: DHA significantly attenuated IL-1β induced proinflammatory IL-8 and IL-6 protein and mRNA in fetal H4, NEC-IEC, and mature Caco2, NCM460 IEC, compared to control and PAL treatment. DHA downregulated IL-1R1 (IL-1β receptor) and NFk β1 mRNA expression in fetal and adult IEC. ARA had potent anti-inflammatory effects with lower IL-8 and IL-6 (protein and mRNA) in fetal H4 but not in NEC-IEC or adult IEC.

Conclusion: The present study provides evidence that DHA and ARA may have important anti-inflammatory functions for prevention of NEC in premature infants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Arachidonic Acid / pharmacology*
  • Caco-2 Cells
  • Cytoprotection
  • Docosahexaenoic Acids / pharmacology*
  • Eicosapentaenoic Acid / pharmacology
  • Enterocolitis, Necrotizing / drug therapy*
  • Enterocolitis, Necrotizing / genetics
  • Enterocolitis, Necrotizing / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Ileum / drug effects*
  • Ileum / embryology
  • Ileum / metabolism
  • Infant, Newborn
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism
  • Palmitic Acid / pharmacology
  • Receptors, Interleukin-1 Type I / genetics
  • Receptors, Interleukin-1 Type I / metabolism

Substances

  • Anti-Inflammatory Agents
  • CXCL8 protein, human
  • IL1R1 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Receptors, Interleukin-1 Type I
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Palmitic Acid
  • Eicosapentaenoic Acid