Elucidation of epigenetic gene regulation mechanism for establishment of new therapeutic strategies for severe infectious diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09580
• 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(信濃町), 講師 (30317333)
• Co-Investigator(Renkei-kenkyūsha): NAKAYAMA Toshinori 千葉大学, 医学部免疫発生学教室, 教授 (50237468)
• Research Collaborator: YAGI Kazuma
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 重症感染症 / エピジェネティクス / インフルエンザ / 肺炎球菌 / ヒストンアセチル化

Outline of Final Research Achievements

The hypothesis of the study was epigenetic mechanism, especially for histone acetylation, might contribute to the poor outcome of post-influenza pneumonia. Mice were infected intranasally with 1.0 × 104 CFU of Streptococcus pneumoniae 7 days after intranasal inoculation with 5 PFU of influenza virus A/PR8.The mice were intraperitoneally injected with the histone deacetylase (HDAC) inhibitor TSA. TSA significantly suppressed HDAC activity and significantly improved the survival rate of mice after post-influenza pneumococcal infection, which was associated with a significant decrease in bacterial load and the total cell count of the BALF. The number of natural killer cells in the lungs were significantly lower in the TSA-treated group, which may contribute to the protective effects of TSA.
TSA protects mice against post-influenza pneumococcal pneumonia possibly through multiple factors, including a decrease in lung and systemic bacterial load, and suppression of systemic inflammation.

Free Research Field

呼吸器内科学