256. EXPRESSION OF 15-LIPOXYGENASE-2 IN THE EPIAIRWAY™ IN VITRO HUMAN TRACHEAL/BRONCHIAL EPITHELIAL MODEL: REGULATION BY TNF-α AND INF-γ.

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Hayden¹, P.J., Jackson¹, G.R., Last¹, T.J., Klausner¹, M., Kubilus¹, J., Shappell², S.B. ¹MatTek Corp., Ashland, MA, ²Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN. The Toxicologist, 66 (1-S), 100, Soc. of Toxicol. (Reston, VA), Abstract #486, (2002).

Summary:
15-Hydroxyeicosatetraenoic acid (15[S]-HETE) is the predominate arachidonic acid (AA) metabolite produced by human tracheal/bronchial tissue. This product of the 15-lipoxygenase (15-LOX) enzyme is believed to play a significant role in human airway inflammation and respiratory diseases including cystic fibrosis and asthma.

In the current work performed by scientists at Vanderbilt University School of Medicine and MatTek Corp., RT-PCR and Western blotting techniques were utilized to investigate the expression of 15-LOX isozymes in EpiAirway™, a commercially available in vitro model of human tracheal/bronchial epithelium.

The effects of TNFα, the TH2 cytokines IL-4 and IL-13, the TH1 cytokine INFγ and various combinations of these cytokines were examined. The previously reported expression of 15-LOX-1, as well as induction of enhanced 15-LOX-1 expression by IL-4 and IL-13, was confirmed by RT-PCR.

Additionally, 15-LOX-2 message and protein were detected in the EpiAirway model. TNFα was found to induce expression of 15-LOX-2 message and protein, while the TH1 cytokine INFγ inhibited the TNFα-induced increase in both message and protein. Identical results were obtained in EpiAirway constructs derived from four separate airway cell donors, including one asthmatic donor.

These results demonstrate, for the first time, 15-LOX-2 expression in human tracheal/bronchial epithelial cells. The induction of 15-LOX-2 by TNFα and inhibition by the TH1 cytokine INFγ suggest a possible important role of 15-LOX-2 in mediating human airways diseases such as asthma, which is characterized by increased TNFα and decreased TH1 (INFγ)/TH2 (IL-4, IL-13) ratios.

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Applications: Asthma, Inflammation - airway

Keywords: 15-HETE, 15-Hydroxy eicosatetraenoic acid (15-HETE), 15-LOX-1, 15-LOX-2, 15-Lipoxygenase, Airway, Arachidonic acid, Asthma, Asthmatic, Asthmatic genotype, Bronchial, Cystic fibrosis, EpiAirway, Gene expression, IL-13, IL-1b, IL-4, INF-gamma, Inflammation, Lipoxygenase, TH1 cytokines, TH2 cytokines, TNF-a, Tracheal

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