Suppression of TGFß-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38-NF-kB Pathway in Carcinoma Cells.

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFß, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFß-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFß and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFß-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFß activities. In addition, SC-1 inhibits TGFß-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.

Association of meteorological factors and air NO2 and O3 concentrations with acute exacerbation of elderly chronic obstructive pulmonary disease.

We studied the combined effect of air pollutant concentrations and meteorological factors [e.g., temperature and atmospheric pressure (AP)] on the acute exacerbation of coronary obstructive pulmonary disease (COPD) in 277 older patients with COPD (240 men and 37 women; average age, 75.3 ± 9.3 years). Average air pollutant concentrations, AP, temperature, and relative humidity corresponding to each of the 7 days before the date of hospitalisation were identified as the case and the two other weekly averages, 4 and 8 weeks prior to admission, were considered the controls. During the warming-up season, COPD exacerbation more likely occurred on days of temperature increase or AP decrease than on other days. Increments in CO, NO2 and O3 concentrations were significantly associated with 5%, 11% and 4% increases in COPD exacerbation risks, respectively. During the cooling-down season, increments in PM10 concentrations were significant risk factors; the exacerbation likely occurred on days of temperature decreases than on other days. Air pollution with increased NO2, CO, O3 and PM10 concentrations and continual temperature changes (colder during cooling-down seasons or hotter during warning-up seasons) were associated with acute exacerbation of COPD in older patients.