HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0802923v1 183/3/1732    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Neveu, W. A. Articles by Rincon, M. PubMed PubMed Citation Articles by Neveu, W. A. Articles by Rincon, M.

IL-6 Is Required for Airway Mucus Production Induced by Inhaled Fungal Allergens¹

Wendy A. Neveu^*, Jenna B. Allard, Oliver Dienz^*, Matthew J. Wargo, Gennaro Ciliberto, Laurie A. Whittaker and Mercedes Rincon^2,*

^* Department of Medicine, Division of Immunobiology, and Department of Medicine, Division of Pulmonary Disease and Critical Care, University of Vermont, Burlington VT 05405; and Istituto di Ricerche di Biologia Molecolare P. Angeletti, Roma, Italy

Allergic asthma is caused by inhaled allergens and is characterized by airway eosinophilia, as well as mucus hypersecretion, which can lead to airflow obstruction. Despite the association of increased IL-6 levels with human atopic asthma, the contribution of IL-6 to the development of allergic airway inflammation triggered by inhaled allergens remains unclear. In this study, we examined the role of IL-6 in a mouse model of allergic airway inflammation induced by direct airway exposure to extracts of Aspergillus fumigatus, a common allergen in humans. We show that inhaled A. fumigatus extracts rapidly trigger the production of IL-6 in the airways. IL-6 appears to be dispensable for the recruitment of eosinophils to the lung during the development of allergic airway inflammation. However, IL-6 is essential for mucus hypersecretion by airway epithelial cells triggered in response to inhaled A. fumigatus Ags. Impaired mucus production caused by IL-6 deficiency correlates with a severe reduction in the levels of IL-13, a major inducer of mucin glycoproteins. Thus, IL-6 is a key regulator of specific hallmark features of allergic airway inflammation and it could be a potential target for pulmonary diseases that are associated with goblet cell metaplasia and mucus hypersecretion.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the National Institutes of Health Grant R01HL69136 (M.R.) and the Center for Biomedical Research Excellence Program of the National Center for Research Resources Grant P20RR15557 (L.W.).

² Address correspondence and reprint requests to: Dr. Mercedes Rincon, Department of Medicine, Division of Immunobiology, Given Medical Building D305, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405. E-mail address: mrincon{at}uvm.edu

³ Abbreviations used in this paper: BALF, bronchoalveolar lavage fluid; A.f., Aspergillus fumigatus; KO, knockout; o.p., oropharyngeal; PAS, periodic acid-Schiff.