Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3

Nature Immunology, 524-31, 2005

Speaker : 藍保欣                       Time : 2005/06/08 14:10~ 15:00

Commentator : 謝奇璋 老師              Place : Room 601

Abstract

Allergy, especially type I allergy such as bronchial asthma, is a major health problem. Prostaglandins, including PGD₂ and PGE₂, are largely produced during the progression of allergy. PGD₂has been recognized as a major mediator of allergic inflammation. However, the NSAID drugs are generally ineffective to suppress the allergic reaction or even induce life-threatening attacks. So the authors supposed the existence of a prostaglandin-dependent pathway that suppresses type 1 allergic reaction in general. In this study, because early studies have described attenuation in various asthmatic responses by PGE₂, so the authors first generated mice deficient in each of the four PGE receptor subtypes (EP1-4) to the ovalbumin–induced asthma model. By measuring some inflammatory indicators to monitor the change of allergic inflammation, they observed enhanced allergic responses in EP3-deficient mice. Next, the authors demonstrated that in wild-type C57BL/6 mice, the allergic inflammation, release of allergen-induced mediator, and expression of allergy-related genes can be suppressed by administrating an EP3-selective agonist, AE-248, after OVA challenge. Again, these results suggest the suppressive role of PGE₂-EP3 signal pathway. Finally, the authors analyzed lung tissue from wild-type C57BL/6 mice and observed that EP3 is constitutively presented on the surface of airway epithelial cells and the gene expression of inflammatory chemokines in this area, such as CCL11 and CCL17, can be suppressed by treating AE-248. These results suggest that PGE₂-EP3 signal pathway suppress allergic inflammation by inhibiting allergen-induced expression of chemokine genes. In short, the authors confirmed the suppressive functions of PGE₂-EP3 signal pathway in the OVA-induced asthma mice model and the concept can be applied to human type 1 allergy, such as bronchial asthma, allergic rhinitis and conjunctivitis.

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