title: Omega-3 PUFA docosahexaenoic acid decreases LPS-stimulated MUC5AC production by altering EGFR-related signaling in NCI-H292 cells.
abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory process characterized by airway mucus hypersecretion. Lipopolysaccharides (LPS) are known to stimulate the production of mucin 5AC (MUC5AC) via epidermal growth factor receptor (EGFR) in human airway cells. Noteworthy, we have previously demonstrated that EGFR/Rac1/reactive oxygen species (ROS)/matrix metalloproteinase 9 (MMP-9) is a key signaling cascade regulating MUC5AC production in airway cells challenged with LPS. Various reports have shown an inverse association between the intake of polyunsaturated fatty acids (PUFA) of the n-3 (omega-3) family or fish consumption and COPD. In the present study, we investigated the influence of docosahexaenoic acid (DHA), one of the most important omega-3 PUFA contained in fish oil, on the production of MUC5AC in LPS-challenged human airway cells NCI--H292. Our results indicate that DHA is capable of counteracting MUC5AC overproduction in LPS-stimulated cells by abrogating both EGFR phosphorylation and its downstream signaling pathway. This signaling pathway not only includes Rac1, ROS and MMP-9, but also NF-κB, since we have found that ROS require NF-κB activity to induce MMP-9 secretion and activation.
authors.affiliation: CBRHC Research Center, Buenos Aires 1426, Argentina.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Binker
authors.affiliation: CBRHC Research Center, Buenos Aires 1426, Argentina.
authors.forename: Makena J
authors.initials: MJ
authors.lastname: Binker-Cosen
authors.affiliation: CBRHC Research Center, Buenos Aires 1426, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Richards
authors.affiliation: CBRHC Research Center, Buenos Aires 1426, Argentina.
authors.forename: Andres A
authors.initials: AA
authors.lastname: Binker-Cosen
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
authors.affiliation: CBRHC Research Center, Buenos Aires 1426, Argentina; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: licb@cbrhc.org.
authors.forename: Laura I
authors.initials: LI
authors.lastname: Cosen-Binker
mesh_terms: D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D055271:Mucin 5AC / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9
keywords: Chronic obstructive pulmonary disease (COPD); Docosahexaenoic acid (DHA); Epidermal growth factor receptor (EGFR); Lipopolysaccharides (LPS); Mucin 5AC (MUC5AC); Polyunsaturated fatty acids (PUFA)