Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells

In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the downregulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-kappaB activation in human melanoma cells.

Prevalence of adult asthma based on questionnaires and methacholine bronchial provocation test in Seoul / 천식및알레르기

BACKGROUND: There have been no reports concerning asthma prevalence in the Korean adult population using objective parameters such as methacholine bronchial provocation tests. OBJECTIVE: The purpose of this study was to evaluate the prevalence of asthma using an objective parameter, and the atopy rate in an adult population living in Seoul. METHOD: A total of 718 subjects (aged from 16 to 70 years) were enrolled in this study. They responded to a modified ATS respiratory questionnaire and underwent methacholine bronchial challenge and skin prick testing to common aeroallergens. RESULTS: The prevalence of current asthma, based on the questionnaire and bronchial challenge, was 3.4%. The prevalences of current asthma and bronchial hyperresponsiveness were higher in subjects over 50 years of age than in those under 50 years of age. The atopy rate, based on the skin prick testing, was 26.9%, and common sensitizing allergens in decreasing frequency were Dermatophagoides farinae (15.5%), D. pteronyssinus (14.2%), Tyrophagus putrescentiae (5.9%), cockroach (5.0%) and Tetranychus urticae (4.9%). CONCLUSION: The prevalence of current asthma and the rate of atopy in an urban adult population were 3.4% and 26.9%, respectively.

A Prospective Study of Asthma Prevalence and Atopy Rate in Children Living in Rural Area of Cheju Island for 3 Years / 소아알레르기및호흡기학회지

PURPOSE: Asthma has been increasing due to changes in life style and indoor environments. Manifestations of asthma and atopy varies according to age. The purpose of this study was to elucidate the changing prevalence of asthma and atopy in children living in rural area of Cheju island via three year prospective study. METHODS: A total of 314 subjects aged from 7 to 12 years was followed up for three years. They responded a ISAAC questionnare, underwent allergy skin prick test with common aeroallergens and methacholine bronchial provocation test. Children with asthma symptoms on a questionnaire and positive methacholine bronchial provocation test were diagnosed as bronchial asthma. Skin prick test was regarded as positive when the size of wheal caused by allergens was same or larger than that caused by histamine. RESULTS: The prevalence of bronchial asthma has a tendency to increase from 4.1 % to 7.3% three years later(P=0.08). The atopy rate has significantly increased from 34.1% to 49.2% in both girls and boys(P<0.001), from 35.0% to 46.9% in girls(P< 0.05), and from 33.3% to 51.3% in boys(P<0.05). The positive skin responses to Dermatophagoides pteronyssinus, D. farinae(P=0.36), Japanese cedar and cockroach were not changed between the three years. However, the postive skin reponse to citrus red mite was significantly increased three years later(from 10.7% to 31.1%, P<0.001). CONCLUSION: The asthma prevalence has a tendency to increase in children living in rural area with citrus farms. The atopy rate has been also increasing in the rural children. These phenomena may be explained by the fact that sensitization to citrus red mite has been increasing when they are getting older.

Association between beta2-adrenoceptor polymorphism and asthma phenotypes in the general population / 천식및알레르기

BACKGROUND: In a previous linkage analysis, a marker locus on chromosome 5q31-33 showed evidence of linkage to bronchial responsiveness to methacholine and atopy. The beta2-adrenoceptor (beta2AR) gene is located on chromosome 5q32 and is considered to be a candidate gene in the development of asthma phenotype. OBJECTIVE: The aim of this study was to evaluate the association between asthma phenotypes and beta2AR polymorphism at amino acids 16 and 27. METHODS: From the general population, 440 unrelated Korean subjects were randomly selected, and asthma phenotypes were determined using a questionnaire, skin prick tests, and methacholine bronchial provocation tests. Haplotypes of 16 and 27 polymorphisms on the beta2AR gene were determined using PCR-based methods. RESULTS: Frequencies of haplotypes of beta2AR gene for polymorphic positions 16 and 27 were Arg16-Gln27:53.2%, Gly16-Gln27:36.4%, Arg16-Glu27:0.1% and Gly16-Glu27:10.3%. No significant association was found between haplotype of beta2AR gene and asthma phenotypes. Among the atopic subjects, however, we observed that Arg16-Gln27 and Gly16-Gln27 haplotypes were significantly associated with nocturnal cough. There was linear association between the development of nocturnal cough and the number of Arg16-Gln27 and Gly16-Gln27 haplotypes, respectively. CONCLUSION: This study demonstrates that the linkage of a gene marker on chromosome 5q31-33 with atopy and bronchial responsiveness is not related with genetic variations in the beta2AR gene. However, beta2AR polymorphisms may play an important role in the expression of nocturnal cough in atopic subjects.