title: In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells.
abstract: Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual's susceptibility to pathogen infection.
authors.affiliation: Department of Natural Science, Colby-Sawyer College , New London, NH , USA.
authors.forename: James
authors.initials: J
authors.lastname: Jukosky
authors.affiliation: Department of Otolaryngology, Dartmouth Hitchcock Medical Center , Lebanon, NH , USA.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Gosselin
authors.affiliation: Department of Natural Science, Colby-Sawyer College , New London, NH , USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Foley
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH , USA.
authors.forename: Tenzin
authors.initials: T
authors.lastname: Dechen
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH , USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Fiering
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH , USA.
authors.forename: Mardi A
authors.initials: MA
authors.lastname: Crane-Godreau
keywords: CCL20; SLPI; antimicrobial peptides; beta defensing-1; cigarette smoke exposure; innate immune response; nasal epithelial cell culture; primary nasal epithelium