title: Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways.
abstract: BACKGROUND
  Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.
  
  
  METHODS
  Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay.
  
  
  RESULTS
  Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1.
  
  
  CONCLUSIONS
  There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America; Department of Integrative Systems Biology, George Washington University, Washington, DC, United States of America; Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Nino
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Shehlanoor
authors.initials: S
authors.lastname: Huseni
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Geovanny F
authors.initials: GF
authors.lastname: Perez
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Krishna
authors.initials: K
authors.lastname: Pancham
authors.affiliation: Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Humaira
authors.initials: H
authors.lastname: Mubeen
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America.
authors.forename: Aleeza
authors.initials: A
authors.lastname: Abbasi
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Eng
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America; Department of Integrative Systems Biology, George Washington University, Washington, DC, United States of America; Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, United States of America; Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC, United States of America.
authors.forename: Anamaris M
authors.initials: AM
authors.lastname: Colberg-Poley
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America; Department of Integrative Systems Biology, George Washington University, Washington, DC, United States of America; Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, United States of America.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Pillai
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, United States of America; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America; Department of Integrative Systems Biology, George Washington University, Washington, DC, United States of America; Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, United States of America; Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC, United States of America.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000378:metabolism* / Q000821:virology; D016022:Case-Control Studies; D002460:Cell Line; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism*; D054414:Chemokine CCL17 / Q000235:genetics / Q000378:metabolism; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012229:Rhinovirus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D054413:Chemokine CCL11; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D016207:Cytokines; D016209:Interleukin-8; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D000094632:Thymic Stromal Lymphopoietin