title: Oleic acid induces lung injury in mice through activation of the ERK pathway.
abstract: Oleic acid (OA) can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1β production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation.
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil. cassianofg@gmail.com
authors.forename: Cassiano Felippe
authors.initials: CF
authors.lastname: Gonçalves-de-Albuquerque
authors.forename: Adriana Ribeiro
authors.initials: AR
authors.lastname: Silva
authors.forename: Patrícia
authors.initials: P
authors.lastname: Burth
authors.forename: Isabel Matos Medeiros
authors.initials: IM
authors.lastname: de Moraes
authors.forename: Flora Magno de Jesus
authors.initials: FM
authors.lastname: Oliveira
authors.forename: Mauricio
authors.initials: M
authors.lastname: Younes-Ibrahim
authors.forename: Maria da Conceição Batista
authors.initials: Mda C
authors.lastname: dos Santos
authors.forename: Heloísa
authors.initials: H
authors.lastname: D'Ávila
authors.forename: Patrícia Torres
authors.initials: PT
authors.lastname: Bozza
authors.forename: Hugo Caire de Castro
authors.initials: HC
authors.lastname: Faria Neto
authors.forename: Mauro Velho de Castro
authors.initials: MV
authors.lastname: Faria
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D055370:Lung Injury / Q000139:chemically induced*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D019301:Oleic Acid / Q000633:toxicity*; D010766:Phosphorylation; D011654:Pulmonary Edema / Q000209:etiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019301:Oleic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D000254:Sodium-Potassium-Exchanging ATPase