Extracellular regulation of interleukin (IL)-1β through lung epithelial cells and defective IL-1 type II receptor expression

Kristin R. Coulter, Mark D. Wewers, Melissa P. Lowe, Daren L. Knoell

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Interleukin (IL)-1β is produced primarily by activated mononuclear phagocytic cells in the lung airway and functions as a potent proinflammatory cytokine. Release of IL-1beta; in the airway microenvironment induces the production of proinflammatory factors from parenchymal airway cells, including IL-8. To study the regulation of lung epithelial cell responsiveness to IL-1β, the human type II-like airway epithelial cell line A549 and primary normal human bronchial epithelial (NHBE) cells were assayed for IL-1-specific response modifiers. Specifically, the IL-1 type I receptor (IL-1RI), IL-1 type II receptor (IL-1RII), TL-1 receptor accessory protein (IL-1RAcP), and IL-1 receptor antagonist (IL-1Ra) were analyzed. Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells. Interestingly, a complete absence of IL-1RII expression was demonstrated under all study conditions in both A549 and NHBE cells. Both cell types were responsive to IL-1β at concentrations as low as 50 to 500 pg/ml when measured by IL-8 release into cell supernatants. IL-1β-induced chemokine production and release were inhibited by a 10-to 1,000-fold molar excess of recombinant IL-1RII or IL-1Ra, whereas IL-1RI was a less effective inhibitor. On the basis of our results, we propose that human lung epithelial cells lack the ability to downregulate IL-1β activity extracellularly because of an inability to express IL-1RII. Release of extracellular IL-1 inhibitors, including soluble IL-1Ra and soluble IL-1RII, by other inflammatory cells present in the airway may be critical for regulation of IL-1β activity in the airway microenvironment.

Original languageEnglish (US)
Pages (from-to)964-975
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume20
Issue number5
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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