Investigation on pathogenesis of COPD exacerbations through autophagy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nippon 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
• 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.

Free Research Field

呼吸器内科学