CD14是表現在單核細胞/巨噬細胞(monocyte/macrophage)細胞膜上的受器，主要功能是辨認革蘭氏陰性菌細胞壁的成分脂多醣(lipopolysaccharide, LPS)，進一步引起宿主細胞先天性免疫(innate immunity)而防禦外來病源菌。在CD14基因啟動子260處有胞嘧啶(Cytosine)和胸腺嘧啶(thymidine)的遺傳變異存在，此變異和發炎疾病的危險因子有關，目前在中風、急性心肌梗塞、慢性牙齦發炎和潰瘍性結腸炎均有正相關的報告。此區域是GC box及Sp蛋白結合位置，帶T allele可能造成DNA和Sp蛋白親合力下降，因此，本篇論文就CD14啟動子-260基因多型性(single nucleotide polymorphism, SNP)在分子基礎上及其在披衣菌感染造成發炎反應上作探討。
我們的結果顯示在台灣CD14基因型的分布如下：TT 27.3%, CT 55.2%, CC 17.5%，TT型的分布比例比其他西方國家高。Chlamydia pneumoiae在CD14/-260三種基因型的盛行率分別如下：TT 78.3%, CT 64.9%, CC 59.5%，TT基因型明顯和Chlamydia pneumoiae感染有關(p=0.029)。在單核球表面CD14表現上，帶TT和CT型者比CC型明顯得高 (分別p=0.034, p=0.044)；而在血漿中水溶性CD14，則是CT型者比CC型高(p=0.046)。在報導基因的分析中，在THP-1細胞CD14/-260T比CD14/-260C增加轉錄活性21.6%，而在HepG2細胞則增加27.3%。以大腸桿菌LPS和披衣菌刺激全血觀察TNFα的產量，發現TT型者比CC型產生的反應高，所以CD14/-260帶TT型的人表現較高的CD14而且在大腸桿菌LPS和披衣菌刺激產生較強的發炎反應。由此研究發現CD14 啟動子260位置單去氧核醣核酸多型性，在調控CD14基因表現和參與披衣菌感染後之發炎及免疫反應扮演極重要角色。

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.

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