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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Yang, Y. Articles by Kelsen, S.G. Search for Related Content PubMed PubMed Citation Articles by Yang, Y. Articles by Kelsen, S.G.

Regulation of interleukin-1ß and interleukin-1ß inhibitor release by human airway epithelial cells

Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Temple University School of Medicine, Philadelphia, PA, USA

CORRESPONDENCE: S.G. Kelsen, 761 Parkinson Pavilion, Temple University Hospital, 3401 N. Broad St., Philadelphia, PA, 19140, USA. Fax: 1 2157071481. E-mail: kelsen@temple.edu

Keywords: Airway inflammation, asthma, cytokines

Received: August 4, 2003
Accepted March 29, 2004

This study was supported, in part, by National Institutes of Health (Bethesda, MD, USA) grant number R01 HL52700-04.

In asthma, human airway epithelial cells (HAECs) regulate the intensity of mucosal inflammation, in part, by releasing the pro-inflammatory cytokine interleukin (IL)-1ß. However, the IL-1ß inhibitors, IL-1 receptor antagonist (IL-1RA) and soluble IL-1 receptor type II (sIL-1RII), regulate IL-1ß bioactivity. In order to better understand the control of IL-1ß activity in the airway mucosa, the role(s) of tumour necrosis factor (TNF)-, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the release of IL-1ß and its inhibitors by cultured HAECs were examined.

HAECs were treated with TNF- (2–200 ng·mL^–1), dibutyryl cAMP (0.01–1 mM), 8-bromo-cGMP (0.01–1 mM) or vehicle for 24 h, and cytokine levels in the HAEC-conditioned medium were measured by enzyme-linked immunosorbent assay.

HAECs produced IL-1ß, IL-1RA and sIL-1RII constitutively, but the inhibitor concentrations greatly exceeded that of IL-1ß (by 100- and 550-fold, respectively). TNF- dose-dependently increased the levels of all IL-1ß cytokine family members. However, over the range of TNF- concentrations studied, IL-1ß concentration increased more than those of its inhibitors. cAMP increased constitutive and TNF--stimulated IL-1ß release but reduced that of sIL-1RII. In contrast, cGMP had no effect on IL-1ß but reduced IL-1RA and sIL-1RII release.

Under basal conditions, the disproportionate release of inhibitors relative to interleukin-1ß by human airway epithelial cells probably prevents interleukin-1ß-mediated biological effects. Tumour necrosis factor-, cyclic adenosine monophosphate and cyclic guanosine monophosphate may potentiate mucosal inflammation by increasing interleukin-1ß levels relative to those of its inhibitors in the airway mucosa.