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Investigation on pathogenesis of COPD exacerbations through autophagy

Research Project

Project/Area Number 24591142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNippon Medical School

Principal Investigator

ISHII Takeo  日本医科大学, 医学部, 講師 (90445750)

Co-Investigator(Kenkyū-buntansha) HAGIWARA Koichi  埼玉医科大学, 医学部, 教授 (00240705)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords慢性閉塞性肺疾患 / 増悪 / オートファジー / NODs / 遺伝子多型 / 自然免疫 / 病態関連遺伝子 / 慢性炎症
Outline of Final Research Achievements

Infections mainly caused exacerbations in chronic obstructive pulmonary disease (COPD). However, the mechanisms in which COPD exacerbations occur remain to be elucidated. We hypothesized that the capacities to recognize bacteria including pseudomonous and streptococcus pneumonia by NODs1 and 2, some of pattern recognition molecules, are intact and still the downstream pathway of NODs for innate immunity including autophagy pathway (ATG16L1 and other autophagy proteins are involved) fail to function in frequent-exacerbators. The expression level of the cytokine IL10 was higher in the monocytes derived from COPD subjects with ATG16L1 300Ala genotype, which was related to frequent exacerbators. A single nucleotide polymorphism rs2075820 in NOD1 was associated with airflow limitation in COPD and NOD1 stimulant was related to the activation of p38 pathway in vitro. Thus, bacterial colonization is thought to promote airflow limitation by NOD1 stimulation and the activation of p38 pathway.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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