Ozone modulates IL-6 secretion in human airway epithelial and smooth muscle cells

Gautam Damera, Hengjiang Zhao, Miao Wang, Michael Smith, Christopher Kirby, William F. Jester, John A. Lawson, Reynold A. Panettieri

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Although ozone enhances leukocyte function and recruitment in airways, the direct effect of ozone in modulating structural cell-derived inflammatory mediators remains unknown. Using a coculture model comprised of differentiated human airway epithelial cells (NHBE) and smooth muscle cells (ASM), we postulate that ozone regulates IL-6 secretion in basal and cytokine-primed structural cells. Air-liquid interface (ALI) cultures of NHBE cells underwent differentiation as determined by mucin secretion, transepithelial electrical resistance (TEER), and ultrastructure parameters. Whereas TNF enhanced basal secretion of IL-6 (57 ± 3%), ozone exposure at 0.6 ppm for 6 h augmented IL-6 levels in basal (41 ± 3%) and TNF- (50 ± 5%) primed cocultures compared with that derived from NHBE or ASM monolayers alone. Levels of PGE2, 6-keto-PGF, PGF, and thromboxane B2 (TxB2) levels in basal and TNF-primed cocultures revealed that ozone selectively enhanced PGE2 production in TNF- (6 ± 3-fold) primed cocultures, with little effect (P > 0.05) on diluent-treated cultures. In accordance with ozone-induced increases in PGE2 levels, cyclooxygenase inhibition with indomethacin partially abolished IL-6 secretion. Surprisingly, indomethacin had little effect on constitutive secretion of IL-6 in cocultures, whereas indomethacin completely restored ozone-mediated TEER reduction in TNF-primed cocultures. Collectively, our data for the first time suggest a dual role of ozone in modulating IL-6 secretion and TEER outcomes in a PGE2-dependent (in presence of TNF stimulus) and -independent manner (in absence of cytokine stimulus).

Original languageEnglish (US)
Pages (from-to)L674-L683
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 1 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Keywords

  • Airway remodeling
  • Asthma
  • Chronic obstructive pulmonary disease
  • Cytokines
  • Inflammation

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