Role of NO in Activation of NFkB by PM 2.5 in Lung Epithelial Cells / 결핵

BACKGROUND:The present study was performed to further improve our understanding of the molecular mechanisms involved in the activation of NFkB, a major transcriptional factor involved in the inflammatory response in the inflammatory response in the lung, by particulate matter in lung epithelial cells wit an aerodynamic diameter of less than 2.5 micro meter(PM2.5). METHODS: Immediate production of reactive oxygen species (ROS) and nitrogen species (RNS), with the PM2.5 induced expression of inducible nitric oxide synthase (iNOS), IkB degradatio and NFkB-dependent transcrptional activity, in A 549 cells, were monitored. Addition, we also examined the effect of the iNOS inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL), on the PM 2.5-induced NFkB activation in A 549 cells. RESULTS:The rapid degradation of IkB and the increase of transcriptional activity of the NFkB-dependent promotor were observed in A 549 cells exposed to PM2.5. The immediate production of ROS in response to PM2.5 in A 549 cells was not clearly detected, although immediate responses were observed in RAW 264.7 cells. A549 cells, cultured in the presence of PM2.5, produced an increase in NO, which was noticeably significant after 15 min of exposure with the expression of iNOS mRNA. The addition of L-NIL, an iNOS inhibitor, significantly inhibited the PM2.5-induced IkB degradation and the increase of the NFkB-dependent transcriptional activity. CONCLUSION: These results suggest that PM2.5 stimulates the immediate production of RNS, leading to the activation of NFkB in the pulmonary epithelium.

Role of NO in Activation of NFkB by PM 2.5 in Lung Epithelial Cells / 결핵

BACKGROUND:The present study was performed to further improve our understanding of the molecular mechanisms involved in the activation of NFkB, a major transcriptional factor involved in the inflammatory response in the inflammatory response in the lung, by particulate matter in lung epithelial cells wit an aerodynamic diameter of less than 2.5 micro meter(PM2.5). METHODS: Immediate production of reactive oxygen species (ROS) and nitrogen species (RNS), with the PM2.5 induced expression of inducible nitric oxide synthase (iNOS), IkB degradatio and NFkB-dependent transcrptional activity, in A 549 cells, were monitored. Addition, we also examined the effect of the iNOS inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL), on the PM 2.5-induced NFkB activation in A 549 cells. RESULTS:The rapid degradation of IkB and the increase of transcriptional activity of the NFkB-dependent promotor were observed in A 549 cells exposed to PM2.5. The immediate production of ROS in response to PM2.5 in A 549 cells was not clearly detected, although immediate responses were observed in RAW 264.7 cells. A549 cells, cultured in the presence of PM2.5, produced an increase in NO, which was noticeably significant after 15 min of exposure with the expression of iNOS mRNA. The addition of L-NIL, an iNOS inhibitor, significantly inhibited the PM2.5-induced IkB degradation and the increase of the NFkB-dependent transcriptional activity. CONCLUSION: These results suggest that PM2.5 stimulates the immediate production of RNS, leading to the activation of NFkB in the pulmonary epithelium.

The Role of TNFalpha Gene Promoter Polymorphism in the Development of Coal Workers' Pneumoconiosis / 대한산업의학회지

OBJECTIVES: This study was performed in order to investigate the frequency of the TNF2 allele in patients with coal workers pneumoconiosis (CWP). METHODS: We compared the genotype distribution of TNFalpha gene promoter polymorphism between 80 CWP patients and 54 healthy controls. RESULTS: The results were as follows : 1. The rare allele TNF2 was significantly more frequent in CWP patients (20.6 %) than in controls (10.2 %). 2. The spontaneous or LPS-induced release of TNFalpha from the peripheral monocytes was slightly increased in the TNF2 group, but these values were not significantly different between groups. 3. In the CWP TNF2 group, the increase of LPS-induced TNFalpha release was significant in comparison with that of the controls. CONCLUSIONS: From the above results, we suggest that the TNF2 allele is strongly associated with susceptibility to CWP development.

Activity of Telomerase in Coal Worker's Autopsied Lung / 대한산업의학회지

OBJECT: We measured the activity of telomerase in coal workers lung tissue and found a significant increase in telomerase activity compared to the control group. Pneumoconiosis has the characteristics of fibroblast proliferation and the accumulation of collagen,thus finally causing the pathologic changes,which lead to the irreversible and progressive fibrosis of the lungs. We hypothesized that this cellular proliferation causing irreversible fibrosis may induce some elongation of the life cycle in the chromosomes and lead to further cellular immortalization. METHOD: 8 postmortem(within 24 hours)pneumo-coniotic cases were examined and their telomerase activity was compared with that of the autopsied lungs of lung cancer patients and of accident victims without any respiratory diseases. Using the extracted ribo-nucleoprotein from pneumoconiotic nodules, telomeric repeat amplification assay (TRAP)was done. RESULT: The pneumoconiotic lungs showed strong telomerase activity, similar to that of the lung cancer patients, while the control group showed no such activity. CONCLUSION: Based on the results of this study, we found that coal dust-induced cellular proliferation affects telomerase-activity clinically.

Autoregulation of Quartz-induced iNOS by iNOS-derived Hydrogen Peroxide in Rat2 Fibroblast / 대한산업의학회지

OBJECTIVES: This study was performed in order to investigate the molecular mechanism regulating nitric oxide synthase(NOS) induced by alpha-quartz in Rat2 fibroblast. METHODS: alpha-quartz-induced nitric oxide(NO) and H2O2 formation and alpha- quartz-induced iNOS protein expression in Rat2 fibroblast were monitored. With iNOS inhibitor(L-N6- (1-iminoethyl)lysine hydrochloride, L-NIL) or antioxidant(catalase), we observed NO and H2O2 formation and iNOS protein expression in Rat2 fibroblast stimulated with alpha-quartz. RESULTS: alpha-quartz stimulated iNOS-induced NO and H2O2 formation in Rat2 fibroblast. L-NIL inhibited H2O2 formation and iNOS protein expression by alpha-quartz in Rat2 fibroblast. Pretreatment with catalase blocked the autoinhibitory pathway of iNOS by iNOSinduced H2O2, therefore H2O2 and NO production and iNOS protein expression were increased in Rat2 fibrobalst stimulated with alpha-quartz CONCLUSIONS: alpha-quartz-induced iNOS stimulated H2O2 formation in Rat2 fibroblast. INOS-induced H2O2 by alpha-quartz plays an important role in the autoinhibition pathway for regulating the iNOS function in Rat2 fibroblast