Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Nakamura M ，Wada H ，Honda K ，Nakamoto K ，Inui T ，Sada M ，Watanabe M ，Takata S ，Yokoyama T ，Saraya T ，Kurai D ，Ishii H ，Goto H ，Kamma H ，Takizawa H ... -  《-》

Dynamic changes of lung sRAGE in mice with chronic obstructive pulmonary disease induced by cigarette smoke exposure.

To study the changes of lung function, pathophysiology, inflammatory cytokines and related inflammatory responses in COPD mouse model, and to analyze the role of sRAGE in the pathogenesis of COPD induced by cigarette smoke (CS) exposure in mice. 24 healthy male C57BL/6J mice aged 6 to 8 weeks were randomly divided into Smoke-Exposed (SE) group and Control group. The mice in SE group were exposed to 7 time points at 3, 7, 15, 30, 60, 90 and 120 days, while mice in control group were exposed to fresh room air, with 3 mice in each group. Lung function of mice was detected at different exposure time points, and the lung tissue sections were stained with HE to observe the lung histopathological changes of mice in each group, and the lung tissue morphological quantitative analysis was performed to evaluate the degree of emphysema. The content of inflammatory cytokines including IL-1β, IL-6 and TNF-α in the supernatant of BALF was detected by ELISA to evaluate the pulmonary inflammation of mice. The expression of sRAGE in BALF supernatant was detected by ELISA. BALF cell precipitates were classified and counted under light microscope. After 90 days of exposure to cigarette smoke, the lung function of mice was significantly reduced, emphysema appeared significantly, and the expression of inflammatory cells and inflammatory cytokines in BALF was significantly increased (all P<0.05). sRAGE increased significantly in the early stage of CS exposure (7-15 days) compared with the control group, and the number of macrophages and levels of inflammatory cytokines in BALF also increased temporarily (P<0.05). With the gradual exposure of CS, sRAGE expression gradually decreased, and was significantly reduced after COPD formation compared with the control group. In the process of the occurrence and development of chronic obstructive pulmonary disease induced by cigarette smoke exposure, the level of sRAGE in bronchoalveolar lavage fluid showed a dynamic change of first increase and then decrease. The expression of sRAGE increased in the early stage of smoke exposure and played a transient pro-inflammatory role. With long-term exposure to cigarette smoke, the inflammatory response is gradually aggravated in lung, and the expression of sRAGE is significantly decreased, and its reduction degree is closely related to the degree of reduced lung function and inflammation.

He Y ，Liang H ，Yang X ，Hao F ，Huang K ，Wang Q ... -  《PLoS One》

Medications for chronic obstructive pulmonary disease: a historical non-interventional cohort study with validation against RCT results.

Wing K ，Williamson E ，Carpenter JR ，Wise L ，Schneeweiss S ，Smeeth L ，Quint JK ，Douglas I ... -  《-》

The effect of tobacco ingredients on smoke chemistry. Part I: Flavourings and additives.

Baker RR ，Pereira da Silva JR ，Smith G 《FOOD AND CHEMICAL TOXICOLOGY》

Correlation between cervical carcinogenesis and tobacco use by sexual partners.

Siokos AG ，Siokou-Siova O ，Tzafetas I 《Hellenic Journal of Nuclear Medicine》