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

• Published in: Pediatric research Vol. 78; no. 6; pp. 626 - 633
• Main Authors: Wijendran, Vasuki, Brenna, J. T., Wang, Dong Hao, Zhu, Weishu, Meng, Di, Ganguli, Kriston, Kothapalli, Kumar S. D., Requena, Pilar, Innis, Sheila, Walker, W. Allan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2015
• Subjects: 631/250; Anti-Inflammatory Agents - pharmacology; Arachidonic Acid - pharmacology; basic-science-investigation; 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; Medicine & Public Health; NF-kappa B p50 Subunit - genetics; NF-kappa B p50 Subunit - metabolism; Palmitic Acid - pharmacology; Pediatric Surgery; Pediatrics; Receptors, Interleukin-1 Type I - genetics; Receptors, Interleukin-1 Type I - metabolism
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/pr.2015.154

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.