Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways

PLoS One. 2014 Dec 29;9(12):e115398. doi: 10.1371/journal.pone.0115398. eCollection 2014.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / metabolism*
  • Asthma / virology
  • Case-Control Studies
  • Cell Line
  • Chemokine CCL11 / genetics
  • Chemokine CCL11 / metabolism*
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / genetics
  • Chemokine CCL22 / metabolism
  • Child
  • Child, Preschool
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / virology
  • RNA, Double-Stranded / pharmacology*
  • Rhinovirus
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CCL11
  • Chemokine CCL17
  • Chemokine CCL22
  • Cytokines
  • Interleukin-8
  • RNA, Double-Stranded
  • Tumor Necrosis Factor-alpha
  • thymic stromal lymphopoietin