Nontypeable Haemophilus influenzae clearance by RAW624.7 cells is impaired by exposure to cigarette smoke extract and the change of inflammatory cell profiles in NTHi challenged whole-body cigarette smoke exposure mice model.

• Main Authors: Chi-Fan Lee, 李啟帆
• Other Authors: 李珍珍
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/tvurmr

碩士 === 中國醫藥大學 === 基礎醫學研究所碩士班 === 105 === From the data released by World Health Organization at 2012, Chronic Obstructive Pulmonary Disease (COPD) causes over three million deaths globally and is climbing up to the third of top ten cause of death at 2012. In many clinical studies, COPD patients usually have symptoms like sputum, long-lasting cough, chronic lung inflammation and air-flow limitation. COPD is an irreversible disease. This condition outdraws the importance of early diagnosis and the proper therapy to COPD. However, COPD is not the top ten cause of death in the low developed countries and undeveloped countries. This condition not only shows the high relation between COPD and the development of a country, but also shows the big health problem in developed country. In addition, the risk factors of COPD could come from air pollution(PM2.5、PM5、PM10、polycyclic aromatic hydrocarbons), cigarette smoke (smoke consumption or second-hand smoke), gene, infection, ageing and so on. In several research studies, cigarette smoke is the major risk factor to trigger COPD. After calculation, over 80 percentage of COPD patient have smoke behavior. Moreover, they are also vulnerable to infection. Nontypeable haemophilus influenzae (NTHi), which is gram-negative coccobacillus bacteria, is the most common pathogen found in sputum from COPD patients. In addition, both cigarette smoke and NTHi infection can lead to lung inflammation, COPD exacerbation and lung cancer. Therefore, we are curious about the immune response and the mechanism of this NTHi infection after cigarette smoke challenge. From the in vitro data, we found bacterial clearance is impaired in cigarette smoke extracts (CSE) treated Raw264.7 cells. The CCL-2, CXCL-2 and CXCL10 mRNA expression were reduced in CSE and NTHi dual treated RAW cells. Moreover, our lab member has previously found that NF-B promoter activity was also attenuated in CSE and NTHi dual treated RAW cells. In order to confirm in vitro results, we set up a whole-body cigarette smoke exposure mouse model. We found cigarette smoke indeed impair lung function within air-flow resistance experiment. The total cells found in BALF were increased in smoke-treated mice or NTHi challenged mice compared to control mice. Yet, this BALF cell increasement was impaired within smoke-treated mice after NTHi challenge.