The Administration of P2Y12 Antagonist (P113) Attenuates Airway hyperresponsiveness and Airway Inflammation in an Ovalbumin (OVA) Specific Allergic Asthma Model

Backgound and OBJECTIVE: Leukotriene E4 contributes to airway inflammation by interacting with P2Y12 receptor as well as type 1 and 2 cysteinyl leukotriene receptors. We investigated the effects of P113, a P2Y12 receptor antagonist, on airway inflammation in a mouse model of allergic asthma. MATERIALS AND METHODS: Sensitized BALB/c mice were intragastrically treated withP113(30mg/kg) 30 minutes before OVA challenge. Airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage (BAL) fluid were evaluated.Human eosinophil EOL-1 cells were treated with LTE4 with or without pre-treatment of P113. Intracellular expression of ECP was evaluated by Western blot, secreted levels of ECP in cell culture supernatant were measured by ELISA. RESULTS: P113 treatment decreased AHR to methacholine and airway inflammatory cell numbers in BAL fluid following OVA challenge (P< 0.01, respectively), attenuated the levels of Th2 cytokine such as Interleukin(IL) -4, IL-5 and IL-13, but not Th1 cytokine in the BAL fluid. The numbers of inflammatory cells in peribronchial and perivascular areas as well as mucus-containing goblet cells weredecreased inP113treated mice compared to vehicle group (P <0.01). LTE4 stimulation decreased intracellular expression but increased secretion of ECP from EOL-1 cells, which was abolished by P113 pre-treatment. CONCLUSION: P113, a P2Y12 receptor antagonistcould prevent the development of AHR, airway inflammation, and cytokine production in allergen challenged mice, affect the activation and function of eosinophils, suggestingthat it may be a novel therapeutic target for asthma treatment.

Author dc:creator

• 서, 동현

Contributors dc:contributor

• 박, 해심
• 대학원 의생명과학과
• 201224386

• Leukotriene E4
• Asthma
• Eosinophil
• Purinergic P2Y12

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000017639
000000017639

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10864