Selective downregulation of prostaglandin E2–related pathways by the TH2 cytokine IL-13 - 20/08/11
Reprint requests: Sally E. Wenzel, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.Denver, Colo
Abstract |
Background |
Levels of COX-2 and downstream products, such as prostaglandin (PG) E2, are increased in inflammatory settings after stimulation by IL-1β, LPS, and other innate factors. Although the TH2 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 PGE2-related pathways nor their effect in primary human airway epithelial cells has been evaluated.
Objective |
To determine the impact of IL-13 on PGE2 pathways in primary human airway epithelial cells.
Methods |
Because PGE2 has anti-inflammatory, antifibrotic, and bronchodilating properties of relevance to asthma, the effect of IL-13 (10 ng/mL for 10 days) on PGE2 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 EP4 were quantified by means of real-time PCR and Western blotting. PGE2 levels in the supernatants were measured by means of enzyme immunoassay.
Results |
IL-13 significantly inhibited the PGE2 synthetic pathways COX-2 and PGE synthase 1 while upregulating the PGE2 metabolizing enzyme 15-PG dehydrogenase. These enzymatic changes associated and correlated with decreased supernatant PGE2 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 PGE2, which might alter inflammatory and immune responses at the level of the epithelium and the submucosa below.
Clinical implications |
Modulation of PGE2 pathways by IL-13 might alter inflammatory and repair processes in asthma.
Le texte complet de cet article est disponible en PDF.Key words : IL-13, prostaglandin E2, COX, asthma
Abbreviations used : ALI, GAPDH, IL-4R⍺, PG, 15-PGDH, STAT
Plan
| Supported by AI-40600 and RR-00051. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 117 - N° 6
P. 1446-1454 - juin 2006 Retour au numéro
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