Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Myeloid differentiation factor 88-dependent signaling is critical for acute organic dust-induced airway inflammation in mice.

Authors
Bauer-C; Kielian-T; Wyatt-TA; Romberger-DJ; West-WW; Gleason-AM; Poole-JA
Source
Am J Respir Cell Mol Biol 2013 Jun; 48(6):781-789
NIOSHTIC No.
20043020
Abstract
Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust-induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-a, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule-1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust-induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by important contributions from upstream TLRs and IL-18R.
Keywords
Organic-dusts; Dusts; Dust-particles; Agriculture; Environmental-exposure; Exposure-levels; Risk-factors; Lung; Respiratory-system-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-disorders; Animals; Proteins; Laboratory-animals; Analytical-processes; Pathology; Metabolism; Author Keywords: MyD88; lung; Toll-like receptor; IL-1R/IL-18R; organic dust
Contact
Jill A. Poole, M.D., Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine, University of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
CODEN
AJRBEL
Publication Date
20130601
Document Type
Journal Article
Email Address
japoole@unmc.edu
Funding Type
Grant; Cooperative Agreement
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008539; Cooperative-Agreement-Number-U54-OH-010162; M082013
Issue of Publication
6
ISSN
1044-1549
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Respiratory Cell and Molecular Biology
State
NE
Performing Organization
University of Nebraska
TOP