ABSTRACT
The number of individuals in the population exposed to biomass fuel smoke (BS) is far greater than the number of cigarette smokers. About 20% of cigarette smokers develop chronic obstructive pulmonary disease (COPD) due to smoke-induced irreversible damage and sustained inflammation of the airway epithelium. However, the role of BS in COPD pathogenesis remains to be elucidated. In this study, we investigated the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 and caspase-1 in the bronchial epithelium from patients with COPD, and further determined the specific role of the NLRP3 inflammasome in bronchial epithelium injury using two in vitro models (BS and cigarette smoke [CS]) in the human bronchial epithelial (HBE) cell line (16HBE). After exposure to BS and CS, the release of damage-associated molecular patterns, the transcriptional and translational up-regulation of NLRP3, and the activation of caspase-1 were observed in cells at different time points. Because IL-1ß secretion was dependent on the NLRP3 inflammasome, we assessed CXCL-8 production in response to smoke. Using a transwell migration assay in which 16HBE cells and human alveolar macrophages were cocultured, we showed that smoke-induced NLRP3 activation in 16HBE cells increased the migration of human alveolar macrophages. When the NLRP3 expression was silenced, the average migration distance of 16HBE was increased in scratch assay, because the activation of NLRP3 induced apoptosis by the p53-Bax mitochondrial pathway in the smoke-induced response. These results demonstrate the importance of the NLRP3 inflammasome in mediating BS- and CS-induced HBE cell damage and proapoptosis.
Subject(s)
Apoptosis , Biomass , Bronchi/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Smoke/adverse effects , Aged , Cell Movement , Cell Proliferation , Cell Survival , Cytokines/metabolism , Demography , Female , Humans , Immunohistochemistry , Inflammation/pathology , Inflammation Mediators/metabolism , Male , Middle Aged , Oxidative Stress , Pulmonary Disease, Chronic Obstructive/pathology , Smoking/adverse effects , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of targeted percutaneous injection of medical ozone through the posterior approach via the spinal canal and dural sac under CT guidance for treatment of lumbar disc herniation.</p><p><b>METHODS</b>In 262 patients with lumbar disc herniation, medical ozone was injected percutaneously under CT guidance into the lumbar intervertebral disc by the posterior approach at paramedian 1-2 cm from the spinous process, targeting the affected lumbar discs, protruded nucleus pulposus and ipsilateral lateral recess. The concentration of ozone was 40-50 µg/ml in the disc/protruded nucleus pulposus and 30 µg/ml in the lateral recess (around the nerve root).</p><p><b>RESULTS</b>The treatment procedures were successfully completed in all the 262 patients. The average scores of JOA and VAS before treatment were 8.30∓1.4 and 8.73∓0.8, and changed significantly to 24.16∓3.2 (P=0.0158) and 2.41∓0.2 (P=0.0242) after treatment, respectively. According to the modified MacNab criteria, the therapeutic effect was excellent in 165 cases, fair in 64 cases, acceptable in 20 cases, and poor in 13 cases, with a total success rate of 87.4%. No patient showed serious complications after the treatment.</p><p><b>CONCLUSION</b>Compared with routine ozone therapy by the posterior-lateral approach, targeted percutaneous ozone injection into the intervertebral disc by the modified posterior approach is safe and yields better therapeutic effect for lumbar disc herniation.</p>
