| Summary: | 碩士 === 國立成功大學 === 醫事技術學系 === 91 === CD14, a pattern recognition receptor on the membrane of monocyte and macrophage, plays a central role in innate immunity through recognition of bacterial lipopolysaccharide (LPS) and initiation of inflammatory response. Recently, CD14/-260C→T gene polymorphism have been found to be a risk related to inflammatory diseases, such as stroke, acute myocardial infarction, chronic periodontitis and ulcerative colitis. The presence of T allele of CD14 promoter may result in decreased affinity of DNA/protein interaction at a GC box that contains a binding site for Sp proteins. The specific goal of our study is to investigate the effects of molecular basis of CD14/-260 polymorphism and its association with chlamydiae-induced chronic inflammatory responses.
Our results revealed that the distribution of CD14 genotypes in Taiwan was as follows: TT 27.3%, CT 55.2%, CC 17.5%. The TT genotype among Taiwanese is higher than that of western countries. Seropositivity for Chlamydia pneumoniae among the three CD14 genotypes was 78.3%, 64.9% and 59.5%, respectively. A significant association of TT genotype with Chlamydia pneumoniae infection was found (p=0.029). The membrane CD14 expression was significantly higher in TT and CT as compared with CC genotypes (p=0.034, p=0.044, respectively), whereas there was a significant higher level of soluble CD14 in CT genotypes than in CC genotypes (p=0.046). In reporter assays, CD14/-260T increased 21.6% and 27.3% transcriptional activity in THP-1 and HepG2, respectively as compared with CD14/-260C. In addition, TNFa production in the whole blood was higher in TT genotype than CC genotype after stimulation by either LPS or Chlamydiae. TT genotypes have increased CD14 expression and stronger inflammation upon LPS and chlamydial stimulation. In conclusion, the single base pair polymorphism at position —260 in the CD14 promoter plays a key role in regulating CD14 expression and mediating chlamydiae-induced inflammatory and immune responses.
|
|---|
