PT  - JOURNAL ARTICLE
AU  - Y. Yang
AU  - W. Bin
AU  - M.O. Aksoy
AU  - S.G. Kelsen
TI  - Regulation of interleukin-1β and interleukin-1β inhibitor release by human airway epithelial cells
AID  - 10.1183/09031936.04.00089703
DP  - 2004 Sep 01
TA  - European Respiratory Journal
PG  - 360--366
VI  - 24
IP  - 3
4099  - http://erj.ersjournals.com/content/24/3/360.short
4100  - http://erj.ersjournals.com/content/24/3/360.full
SO  - Eur Respir J2004 Sep 01; 24
AB  - In asthma, human airway epithelial cells (HAECs) regulate the intensity of mucosal inflammation, in part, by releasing the pro-inflammatory cytokine interleukin (IL)-1β. However, the IL-1β inhibitors, IL-1 receptor antagonist (IL-1RA) and soluble IL-1 receptor type II (sIL-1RII), regulate IL-1β bioactivity. In order to better understand the control of IL-1β activity in the airway mucosa, the role(s) of tumour necrosis factor (TNF)-α, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the release of IL-1β and its inhibitors by cultured HAECs were examined. HAECs were treated with TNF-α (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-1β, IL-1RA and sIL-1RII constitutively, but the inhibitor concentrations greatly exceeded that of IL-1β (by ∼100- and ∼550-fold, respectively). TNF-α dose-dependently increased the levels of all IL-1β cytokine family members. However, over the range of TNF-α concentrations studied, IL-1β concentration increased more than those of its inhibitors. cAMP increased constitutive and TNF-α-stimulated IL-1β release but reduced that of sIL-1RII. In contrast, cGMP had no effect on IL-1β but reduced IL-1RA and sIL-1RII release. Under basal conditions, the disproportionate release of inhibitors relative to interleukin-1β by human airway epithelial cells probably prevents interleukin-1β-mediated biological effects. Tumour necrosis factor-α, cyclic adenosine monophosphate and cyclic guanosine monophosphate may potentiate mucosal inflammation by increasing interleukin-1β levels relative to those of its inhibitors in the airway mucosa. This study was supported, in part, by National Institutes of Health (Bethesda, MD, USA) grant number R01 HL52700-04.