The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation
| العنوان: | The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation |
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| المؤلفون: | David E. Kling, Yingying He, David R. Hill, Nathan Lawlor, David S. Newburg, Yi Huang, Shubai Liu, Samuel B Feinberg, Serena Leone |
| المساهمون: | He, Yingying, Liu, Shubai, Kling, David E, Leone, Serena, Lawlor, Nathan T, Huang, Yi, Feinberg, Samuel B, Hill, David R, Newburg, David S. |
| المصدر: | Gut. 65:33-46 |
| بيانات النشر: | BMJ, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Lipopolysaccharides, 0301 basic medicine, Lipopolysaccharide Receptors, Enzyme-Linked Immunosorbent Assay, Inflammation, BACTERIAL PATHOGENESIS, Biology, Cell Line, Microbiology, Proinflammatory cytokine, BREAST MILK, Mice, 03 medical and health sciences, chemistry.chemical_compound, 2'-Fucosyllactose, INFLAMMATION, medicine, Animals, Enterotoxigenic Escherichia coli, Humans, Escherichia coli Infections, Innate immune system, Milk, Human, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-8, Gastroenterology, Flow Cytometry, MUCOSAL IMMUNOLOGY, OLIGOSACCHARIDES, Mice, Inbred C57BL, Toll-Like Receptor 4, Enterocytes, 030104 developmental biology, chemistry, Mucosal immunology, TLR4, Female, Macrophage migration inhibitory factor, medicine.symptom, Trisaccharides, Breast feeding |
| الوصف: | Background A major cause of enteric infection, Gram-negative pathogenic bacteria activate mucosal inflammation through lipopolysaccharide (LPS) binding to intestinal toll-like receptor 4 (TLR4). Breast feeding lowers risk of disease, and human milk modulates inflammation. Objective This study tested whether human milk oligosaccharides (HMOSs) influence pathogenic Escherichia coli -induced interleukin (IL)-8 release by intestinal epithelial cells (IECs), identified specific proinflammatory signalling molecules modulated by HMOSs, specified the active HMOS and determined its mechanism of action. Methods Models of inflammation were IECs invaded by type 1 pili enterotoxigenic E. coli (ETEC) in vitro: T84 modelled mature, and H4 modelled immature IECs. LPS-induced signalling molecules co-varying with IL-8 release in the presence or absence of HMOSs were identified. Knockdown and overexpression verified signalling mediators. The oligosaccharide responsible for altered signalling was identified. Results HMOSs attenuated LPS-dependent induction of IL-8 caused by ETEC, uropathogenic E. coli , and adherent-invasive E. coli (AIEC) infection, and suppressed CD14 transcription and translation. CD14 knockdown recapitulated HMOS-induced attenuation. Overexpression of CD14 increased the inflammatory response to ETEC and sensitivity to inhibition by HMOSs. 2′-fucosyllactose (2′-FL), at milk concentrations, displayed equivalent ability as total HMOSs to suppress CD14 expression, and protected AIEC-infected mice. Conclusions HMOSs and 2′-FL directly inhibit LPS-mediated inflammation during ETEC invasion of T84 and H4 IECs through attenuation of CD14 induction. CD14 expression mediates LPS-TLR4 stimulation of portions of the ‘macrophage migration inhibitory factors’ inflammatory pathway via suppressors of cytokine signalling 2/signal transducer and activator of transcription 3/NF-κB. HMOS direct inhibition of inflammation supports its functioning as an innate immune system whereby the mother protects her vulnerable neonate through her milk. 2′-FL, a principal HMOS, quenches inflammatory signalling. |
| تدمد: | 1468-3288 0017-5749 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4317ca0bdeb277531d03ee4839e0e577Test https://doi.org/10.1136/gutjnl-2014-307544Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4317ca0bdeb277531d03ee4839e0e577 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14683288 00175749 |
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