title: DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling.
abstract: Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. Primary macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch 1 and Jagged 1 protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box 1 and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch 1/Jagged 1 protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Mehboob
authors.initials: M
authors.lastname: Ali
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Heyob
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.|Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D018496:Hyperoxia / Q000276:immunology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008809:Mice, Inbred C3H; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D024243:HMGB1 Protein; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D004281:Docosahexaenoic Acids