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


CONCLUSIONS
The present study provides evidence that DHA and ARA may have important anti-inflammatory functions for prevention of NEC in premature infants.
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
Vasuki
V
Wijendran
Division of Nutritional Sciences, Cornell University, Ithaca, New York.
J T
JT
Brenna
Division of Nutritional Sciences, Cornell University, Ithaca, New York.
Dong Hao
DH
Wang
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
Weishu
W
Zhu
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
Di
D
Meng
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
Kriston
K
Ganguli
Division of Nutritional Sciences, Cornell University, Ithaca, New York.
Kumar S D
KS
Kothapalli
Liverpool School of Tropical Medicine, Liverpool, UK.
Pilar
P
Requena
Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Sheila
S
Innis
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
W Allan
WA
Walker
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology*; D018938:Caco-2 Cells; D019610:Cytoprotection; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007082:Ileum / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; C508590:IL1R1 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D053573:Receptors, Interleukin-1 Type I; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019308:Palmitic Acid; D015118:Eicosapentaenoic Acid