title: Formaldehyde inhalation during pregnancy abolishes the development of acute innate inflammation in offspring.
abstract: Formaldehyde (FA) is an environmental and occupational pollutant that induces programming mechanisms on the acquired immune host defense in offspring when exposed during the prenatal period. Hence, here we investigated whether the exposure of FA on pregnant rats could affect the development of an innate acute lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant Wistar rats were exposed to FA (0.92 mg/m(3)) or vehicle (distillated water), both 1 h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats were used as control. After 30 days of birth, the offspring was submitted to injection of LPS (Salmonella abortus equi, 5 mg/kg, i.p.). Systemic and lung inflammatory parameters were evaluated 24 h later. Exposure to FA during gestation abolished the development of acute lung injury in offspring, as observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in the blood and in the bone marrow, and decreased myeloperoxidase activity in the lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced oxidative burst. Alterations on the profile of inflammatory cytokines were evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear factor-kappa B translocation into the nucleus were also reduced. Additionally, hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA exposed mothers. Together, our data clearly show that FA exposure in the prenatal period modifies the programming mechanisms of the innate defense in the offspring leading to impaired defense against infections.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Silva Ibrahim
authors.affiliation: Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Miranda da Silva
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Éric Diego
authors.initials: ÉD
authors.lastname: Barioni
authors.affiliation: Department of Immunology, University of São Paulo, São Paulo, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: Correa-Costa
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Carine Cristiane
authors.initials: CC
authors.lastname: Drewes
authors.affiliation: Department of Immunology, University of São Paulo, São Paulo, Brazil.
authors.forename: Niels Olsen
authors.initials: NO
authors.lastname: Saraiva Câmara
authors.affiliation: Department of Pharmacology, University of São Paulo, São Paulo, Brazil.
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares-de-Lima
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra Helena
authors.initials: SH
authors.lastname: Poliselli Farsky
authors.affiliation: Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-dos-Santos-Franco
mesh_terms: D021581:Active Transport, Cell Nucleus; D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D005786:Gene Expression Regulation; D005865:Gestational Age; D007113:Immunity, Innate / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005557:Formaldehyde
keywords: Acute lung injury; Cytokines; LPS; NF-kappa B; Oxidative burst; Pollutants; Toll-like receptor 4 (TLR4)