BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™
Europe
Asia

DIVERSITY

PROFILES
Company Profiles

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Research Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Immunology - Infectious Diseases - Microbiology - Respiratory Medicine - Virology

IL-1a/IL-1R1 Expression in Chronic Obstructive Pulmonary Disease and Mechanistic Relevance to Smoke-Induced Neutrophilia in Mice
Published: Tuesday, December 06, 2011
Author: Fernando M. Botelho et al.

by Fernando M. Botelho, Carla M. T. Bauer, Donna Finch, Jake K. Nikota, Caleb C. J. Zavitz, Ashling Kelly, Kristen N. Lambert, Sian Piper, Martyn L. Foster, James J. P. Goldring, Jadwiga A. Wedzicha, Jennifer Bassett, Jonathan Bramson, Yoichiro Iwakura, Matthew Sleeman, Roland Kolbeck, Anthony J. Coyle, Alison A. Humbles, Martin R. Stämpfli

Background

Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide. Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.

Methodology and Principal Findings

The objective of this study was to assess IL-1 a and ß expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation. Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1a and ß. Here, we demonstrate an underappreciated role for IL-1a expression in COPD. While a strong correlation existed between IL-1a and ß levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1a-dependent, and IL-1ß- and caspase-1-independent in a murine model of cigarette smoke exposure. As IL-1a was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1a+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation. IL-1a/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.

Conclusions and Significance

This study provides compelling evidence that IL-1a is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1a/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD.

  More...