Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways

Authors

Gustavo Nino, George Washington UniversityFollow
Shehlanoor Huseni, Children's National Medical Center
Geovanny F. Perez, Children's National Medical CenterFollow
Krishna Pancham, Children's National Medical Center
Humaira Mubeen, Children's National Medical Center
Aleeza Abeesi, Children's National Medical Center
Justin Wang, Children's National Medical CenterFollow
Stephen Eng, Children's National Medical Center
Anamaris M. Colberg-Poley, George Washington UniversityFollow
Mary C. Rose, George Washington UniversityFollow

Document Type

Journal Article

Publication Date

12-29-2014

Journal

PLoS ONE

Volume

Volume 9, Issue 12

Inclusive Pages

Article number e115398

DOI

10.1371/journal.pone.0115398

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.

Comments

Reproduced with permission of PLoS ONE.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

APA Citation

Nino, G., Huseni, S., Perez, G.F., Pancham, K., Mubeen, H., et al. (2014) Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways. PLoS ONE 9(12): e115398.

Peer Reviewed

1

Open Access

1