Emodin Attenuates Cigarette Smoke Induced Lung Injury in a Mouse Model via Suppression of Reactive Oxygen Species Production

Emodin has antioxidative activities. Here, we investigated the effects of emodin on cigarette smoke (CS)‐induced acute lung inflammation. Mice (C57BL/6) were exposed to CS. Emodin was administrated with intraperitoneal bolus injection of emodin (20 or 40 mg/kg) daily 1 h before CS exposure. Emodin inhibited CS‐induced inflammatory cells infiltration in mouse lungs, especially at 40 mg/kg. Moreover, emodin resulted in significant reductions in total bronchoalveolar lavage fluid (BALF) cells, as compared with air exposure control, coupled with decreases in BALF cytokines. The activities of superoxide dismutase, catalase, and glutathione peroxidase were remarkably enhanced by emodin in CS‐exposed mice. Emodin enhanced CS‐induced expression of heme oxygenase‐1 and nuclear factor‐erythroid 2‐related factor‐2 (both are antioxidative genes) at both mRNA and protein levels, and profoundly promoted their activities in CS‐treated mice. Collectively, our results suggested that emodin protects mouse lung from CS‐induced lung inflammation and oxidative damage, most likely through its antioxidant activity.     

IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation

Th1 inflammation and remodeling characterized by local tissue destruction coexist in pulmonary emphysema and other diseases. To test the hypothesis that IL-18 plays an important role in these responses, we characterized the regulation of IL-18 in lungs from cigarette smoke (CS) and room air-exposed mice and characterized the effects of CS in wild-type mice and mice with null mutations of IL-18Ralpha (IL-18Ralpha(-/-)). CS was a potent stimulator and activator of IL-18 and caspases 1 and 11. In addition, although CS caused inflammation and emphysema in wild-type mice, both of these responses were significantly decreased in IL-18Ralpha(-/-) animals. CS also induced epithelial apoptosis, activated effector caspases and stimulated proteases and chemokines via IL-18Ralpha-dependent pathways. Importantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macrophages from smokers and patients with chronic obstructive lung disease. Elevated levels of circulating IL-18 were also seen in patients with chronic obstructive lung disease. These studies demonstrate that IL-18 and the IL-18 pathway are activated in CS-exposed mice and man. They also demonstrate, in a murine modeling system, that IL-18R signaling plays a critical role in the pathogenesis of CS-induced inflammation and emphysema.     

Notch3对促进胰腺星形细胞活化的基因表达及信号通路的影响

目的:分离培养小鼠胰腺星形细胞(PSCs),检测Notch3对促进PSCs活化的基因表达及信号通路的影响.方法:对小鼠PSCs进行分离培养及传代.采用免疫荧光染色检测活化的小鼠PSCs中α-SMA,fibronectin及collagen Ⅰ的表达;细胞分组为空白对照组(MOCK组),阴性对照组(转染Notch3 si...     

Influence of antibiotics on intestinal tract survival and translocation of environmental Pseudomonas species

The environmental release of microorganisms has prompted the investigation of potential health effects associated with their release. In this study, survival and translocation to the spleen and liver of several environmental Pseudomonas spp. were investigated in antibiotic-treated mice. Pseudomonas aeruginosa BC16 and P. maltophilia BC6, isolated from a commercial product for polychlorinated biphenyl degradation; P. aeruginosa AC869, a 3,5-dichlorobenzoate degrader; and P. cepacia AC1100, an organism that metabolizes 2,4,5-trichlorophenoxyacetic acid were examined for their survival capabilities in the intestines of mice dosed with clindamycin, kanamycin, rifampin, or spectinomycin. A mouse intestinal isolate, strain PAMG, was included in the study. Following antibiotic pretreatment (1 mg twice daily for 3 days), mice were dosed by gavage with 10(9) CFU of each Pseudomonas strain. At the end of the 5-day test period, strains AC869 and PAMG survived in kanamycin-, rifampin-, spectinomycin-, and clindamycin-treated animals. A statistically significant (P less than 0.05) increase in survival of strain PAMG was observed in clindamycin-, kanamycin-, and spectinomycin-treated mice for the test period. Treatment with clindamycin or rifampin increased (P less than 0.05) survival of strain BC6, an organism resistant to both antibiotics. However, strain BC6 was detected only in rifampin-treated mice at the end of the 5-day test period. Strain BC16, a clindamycin-resistant strain, was detected in clindamycin-treated mice and the untreated control animals. Rifampin had a negative effect (P less than 0.05) on strain AC869 and PAMG survival. Translocation to the spleen was observed in spectinomycin- and clindamycin-treated mice but was not detected in kanamycin- or rifampin-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of antibiotics on intestinal tract survival and translocation of environmental Pseudomonas species.

The environmental release of microorganisms has prompted the investigation of potential health effects associated with their release. In this study, survival and translocation to the spleen and liver of several environmental Pseudomonas spp. were investigated in antibiotic-treated mice. Pseudomonas aeruginosa BC16 and P. maltophilia BC6, isolated from a commercial product for polychlorinated biphenyl degradation; P. aeruginosa AC869, a 3,5-dichlorobenzoate degrader; and P. cepacia AC1100, an organism that metabolizes 2,4,5-trichlorophenoxyacetic acid were examined for their survival capabilities in the intestines of mice dosed with clindamycin, kanamycin, rifampin, or spectinomycin. A mouse intestinal isolate, strain PAMG, was included in the study. Following antibiotic pretreatment (1 mg twice daily for 3 days), mice were dosed by gavage with 10(9) CFU of each Pseudomonas strain. At the end of the 5-day test period, strains AC869 and PAMG survived in kanamycin-, rifampin-, spectinomycin-, and clindamycin-treated animals. A statistically significant (P less than 0.05) increase in survival of strain PAMG was observed in clindamycin-, kanamycin-, and spectinomycin-treated mice for the test period. Treatment with clindamycin or rifampin increased (P less than 0.05) survival of strain BC6, an organism resistant to both antibiotics. However, strain BC6 was detected only in rifampin-treated mice at the end of the 5-day test period. Strain BC16, a clindamycin-resistant strain, was detected in clindamycin-treated mice and the untreated control animals. Rifampin had a negative effect (P less than 0.05) on strain AC869 and PAMG survival. Translocation to the spleen was observed in spectinomycin- and clindamycin-treated mice but was not detected in kanamycin- or rifampin-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)