Document Type
Article
Journal Title
Respiratory research
Publication Date
Fall 9-16-2015
Volume
16
Abstract
Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in MyD88 KO tracheal epithelial cells as compared to wild type (WT) control. Similarly, the normative ODE-induced slowing of cell migration in response to wound repair was aberrant in MyD88 KO cells. Next, we created MyD88 bone marrow chimera mice to investigate the relative contribution of MyD88-dependent signaling in lung resident (predominately epithelial cells) versus hematopoietic cells. Importantly, we demonstrate that ODE-induced airway hyperresponsiveness is MyD88-dependent in lung resident cells, whereas MyD88 action in hematopoietic cells is mainly responsible for ODE-induced TNF-α release. MyD88 signaling in lung resident and hematopoietic cells are necessary for ODE-induced IL-6 and neutrophil chemoattractant (CXCL1 and CXCL2) release and neutrophil influx. Collectively, these findings underscore an important role for MyD88 in lung resident cells for regulating ciliary motility, wound repair and inflammatory responses to ODE, and moreover, show that airway hyperresponsiveness appears uncoupled from airway inflammatory consequences to organic dust challenge in terms of MyD88 involvement.
MeSH Headings
Airway Resistance, Animals, Antigens, CD45, Bone Marrow Transplantation, Bronchoconstriction, Cell Movement, Cilia, Cytokines, Dust, Electric Impedance, Epithelial Cells, Genotype, Hematopoietic Stem Cells, Housing, Animal, Inflammation Mediators, Inhalation Exposure, Lung, Lung Compliance, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88, Neutrophil Infiltration, Organic Chemicals, Phenotype, Pneumonia, Signal Transduction, Swine, Time Factors
DOI Link
ISSN
1465-993X
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Poole, Jill A.; Wyatt, Todd A.; Romberger, Debra J.; Staab, Elizabeth; Simet, Samantha; Reynolds, Stephen J.; Sisson, Joseph H.; and Kielian, Tammy, "MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment." (2015). Journal Articles: Pulmonary & Critical Care Med. 4.
https://digitalcommons.unmc.edu/com_pulm_articles/4
Included in
Allergy and Immunology Commons, Critical Care Commons, Respiratory System Commons, Respiratory Tract Diseases Commons