Investigation of immune mechanism of PGD2/CRTH2 in severe infectious diseases

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Keio University
• Principal Investigator: ISHII MAKOTO 慶應義塾大学, 医学部, 講師 (30317333)
• Co-Investigator(Renkei-kenkyūsha): FUJII Hideki 琉球大学, 医学研究科, 准教授 (50356250)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: CRtH2 / 敗血症 / エピジェネティクス / プロスタグランジンD2

Outline of Final Research Achievements

We evaluated the role of CRTH2 using a mice model of polymicrobial sepsis. CRTH2 knockout (-/-) mice were highly resistant to sepis and peritoneal bacterilal load in CRTH2-/- mice was significantly lower as compared to that in wild-type mice.Pharmacological inhibition of Gr-1, a neutrophil marker, and CXCR2 attenuated the protective effects aganist sepsis in CRTH2-/- mice, indicating that CXCR2-expressing neutrophils play protective roles in CRTH2-/- mice in this sepsis model. Moreover, acetylation of histone H3 at CXCR2 promoter in perippheral neutrophils was reduced 2 h after the surgery in wild-type neutrophils, while that in CRTH2-/- mice was not reduced 2 h after the surgery, suggesting that CXCR2 expression is regulated by epigenetic change.

Free Research Field

感染免疫学