title: Regulation of interleukin-1beta and interleukin-1beta inhibitor release by human airway epithelial cells.
abstract: In asthma, human airway epithelial cells (HAECs) regulate the intensity of mucosal inflammation, in part, by releasing the pro-inflammatory cytokine interleukin (IL)-1beta. However, the IL-1beta inhibitors, IL-1 receptor antagonist (IL-1RA) and soluble IL-1 receptor type II (sIL-1RII), regulate IL-1beta bioactivity. In order to better understand the control of IL-1beta activity in the airway mucosa, the role(s) of tumour necrosis factor (TNF)-alpha, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the release of IL-1beta and its inhibitors by cultured HAECs were examined. HAECs were treated with TNF-alpha (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-1beta, IL-1RA and sIL-1RII constitutively, but the inhibitor concentrations greatly exceeded that of IL-1beta (by approximately 100- and approximately 550-fold, respectively). TNF-alpha dose-dependently increased the levels of all IL-1beta cytokine family members. However, over the range of TNF-alpha concentrations studied, IL-1beta concentration increased more than those of its inhibitors. cAMP increased constitutive and TNF-alpha-stimulated IL-1beta release but reduced that of sIL-1RII. In contrast, cGMP had no effect on IL-1beta but reduced IL-1RA and sIL-1RII release. Under basal conditions, the disproportionate release of inhibitors relative to interleukin-1beta by human airway epithelial cells probably prevents interleukin-1beta-mediated biological effects. Tumour necrosis factor-alpha, cyclic adenosine monophosphate and cyclic guanosine monophosphate may potentiate mucosal inflammation by increasing interleukin-1beta levels relative to those of its inhibitors in the airway mucosa.
authors.affiliation: 761 Parkinson Pavilion, Temple University Hospital, 3401 N. Broad St., Philadelphia, PA, 19140, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Bin
authors.forename: M O
authors.initials: MO
authors.lastname: Aksoy
authors.forename: S G
authors.initials: SG
authors.lastname: Kelsen
mesh_terms: D001249:Asthma / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003995:Dibutyryl Cyclic GMP; D000242:Cyclic AMP; D006152:Cyclic GMP