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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/L674    most recent 90585.2008v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Damera, G. Articles by Panettieri, R. A. Search for Related Content PubMed PubMed Citation Articles by Damera, G. Articles by Panettieri, R. A., Jr.

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

¹Pulmonary, Allergy, and Critical Care Division, Department of Medicine, ²Department of Pharmacology, and ³Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia; and ⁴Department of Chemical Engineering, Villanova University, Villanova, Pennsylvania

Submitted 25 November 2008 ; accepted in final form 2 February 2009

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-PGF₁, PGF₂, 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).

asthma; airway remodeling; inflammation; cytokines; chronic obstructive pulmonary disease