Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 117, Issue 6, Pages 1446-1454Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2006.01.049
Keywords
IL-13; prostaglandin E-2; COX; asthma
Categories
Funding
- NCRR NIH HHS [RR00051] Funding Source: Medline
- NIAID NIH HHS [AI-40600] Funding Source: Medline
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Background: Levels of COX-2 and downstream products, such as prostaglandin (PG) E-2, are increased in inflammatory settings after stimulation by IL-1 beta, LPS, and other innate factors. Although the T(H)2 cytokines IL-4 and IL-13 have been reported to decrease COX-2 levels in some cell types, neither the effect of these cytokines on other PGE(2)-related pathways nor their effect in primary human airway epithelial cells has been evaluated. Objective: To determine the impact of IL-13 on PGE(2) pathways in primary human airway epithelial cells. Methods: Because PGE(2) has anti-inflammatory, antifibrotic, and bronchodilating properties of relevance to asthma, the effect of IL-13 (10 ng/mL for 10 days) on PGE(2) pathway elements in first-passage air-liquid interface epithelial cells from 8 endobronchial brushings (5 asthmatic subjects and 3 healthy subjects) was evaluated. mRNA and protein levels for COX-1 and COX-2, membrane-bound PGE synthase 1, 15-PG dehydrogenase, and the receptors EP2 and EN were quantified by means of real-time PCR and Western blotting. PGE(2) levels in the supernatants were measured by means of enzyme immunoassay. Results: IL-13 significantly inhibited the PGE(2) synthetic pathways COX-2 and PGE synthase I while upregulating the PGE(2) metabolizing enzyme 15-PG dehydrogenase. These enzymatic changes associated and correlated with decreased supernatant PGE(2) levels. Significant reductions in the mRNA for EP2 (but not EP4) were also observed. Changes in the PG pathway were both time and dose dependent (n = 3). Conclusion: These data suggest that IL-13 induces systematic modulation of proteins related to the production, catabolism, and function of PGE(2), which might alter inflammatory and immune responses at the level of the epithelium and the submucosa below. Clinical implications: Modulation of PGE(2) pathways by IL-13 might alter inflammatory and repair processes in asthma.
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