title: Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation.
abstract: Parental, particularly maternal, smoking increases the risk for childhood allergic asthma and infection. Similarly, in a murine allergic asthma model, prenatal plus early postnatal exposure to secondhand cigarette smoke (SS) exacerbates airways hyperreactivity and Th2 responses in the lung. However, the mechanism and contribution of prenatal versus early postnatal SS exposure on allergic asthma remain unresolved. To identify the effects of prenatal and/or early postnatal SS on allergic asthma, BALB/c dams and their offspring were exposed gestationally and/or 8-10 wk postbirth to filtered air or SS. Prenatal, but not postnatal, SS strongly increased methacholine and allergen (Aspergillus)-induced airway resistance, Th2 cytokine levels, and atopy and activated the Th2-polarizing pathway GATA3/Lck/ERK1/2/STAT6. Either prenatal and/or early postnatal SS downregulated the Th1-specific transcription factor T-bet and, surprisingly, despite high levels of IL-4/IL-13, dramatically blocked the allergen-induced mucous cell metaplasia, airway mucus formation, and the expression of mucus-related genes/proteins: Muc5ac, γ-aminobutyric acid A receptors, and SAM pointed domain-containing Ets-like factor. Given that SS/nicotine exposure of normal adult mice promotes mucus formation, the results suggested that fetal and neonatal lung are highly sensitive to cigarette smoke. Thus, although the gestational SS promotes Th2 polarization/allergic asthma, it may also impair and/or delay the development of fetal and neonatal lung, affecting mucociliary clearance and Th1 responses. Together, this may explain the increased susceptibility of children from smoking parents to allergic asthma and childhood respiratory infections.
authors.affiliation: Respiratory Immunology Division, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Shashi P
authors.initials: SP
authors.lastname: Singh
authors.forename: Sravanthi
authors.initials: S
authors.lastname: Gundavarapu
authors.forename: Juan C
authors.initials: JC
authors.lastname: Peña-Philippides
authors.forename: Jules
authors.initials: J
authors.lastname: Rir-Sima-ah
authors.forename: Neerad C
authors.initials: NC
authors.lastname: Mishra
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wilder
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Langley
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Smith
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Sopori
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D020545:Respiratory Mucosa / Q000196:embryology / Q000276:immunology* / Q000473:pathology; D012307:Risk Factors; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D014028:Tobacco Smoke Pollution