Antioxidant-sensitive regulation of inflammatory-response genes in Kaposi's sarcoma cells.
Antioxidant-sensitive regulation of inflammatory-response genes in Kaposi's sarcoma cells.
复制标题
卡波西肉瘤细胞中炎症反应基因的抗氧化敏感调节。
DOI：
10.1097/00042560-199609000-00001
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Medford,RM
中科院分区：
文献类型：
--
作者：
Offermann,MK;Lin,JC;Mar,EC;Shaw,R;Yang,J;Medford,RM
卡波西肉瘤（KS）是一种多灶性血管病变，其特征是内皮样KS细胞异常增殖，并伴有明显的白细胞浸润。KS病变包含新的疱疹样DNA序列，KSHV，假设起源于KS的病毒病原体。利用保留KSHV序列的培养的KS细胞，多种信号，包括肿瘤坏死因子α、白细胞介素（IL） 1β、多肌苷酸/多胞苷酸和脂多糖，诱导细胞因子IL-6和参与白细胞募集的细胞粘附分子的表达，包括血管粘附分子1 （VCAM-1）和细胞间粘附分子1 （ICAM-1）。巯基抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC）选择性抑制KS细胞中bbb90 %的核因子κ b样DNA结合活性的激活。在KS细胞中，PDTC在mRNA、蛋白和功能水平上也使诱导的VCAM-1和IL-6水平降低了约85%。相比之下，PDTC没有抑制ICAM-1或E-selectin的诱导表达。这些研究表明，PDTC在含有KSHV的KS细胞中差异调节炎症反应基因的表达，表明还原-氧化敏感事件参与了这些基因的调控。这些研究还表明，巯基抗氧化剂如PDTC可能通过阻止可能参与KS发病机制的特异性炎症反应基因的诱导，在治疗KS中发挥潜在的治疗作用。
Kaposi's sarcoma (KS) is a multifocal vascular lesion characterized by abnormal proliferation of endothelial-like KS cells linked to a pronounced leukocyte infiltration. KS lesions contain novel herpes-like DNA sequences, KSHV, hypothesized to originate from the viral pathogen for KS. Using cultured KS cells that retain the KSHV sequences, diverse signals, including tumor necrosis factor alpha, interleukin (IL) 1β, polyinosinic acid/polycytidylic acid, and lipopolysaccharide, induced the expression of the cytokine IL-6 and cellular adhesion molecules involved in leukocyte recruitment, including vascular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The thiol-antioxidant pyrrolidine dithiocarbamate (PDTC) selectively inhibited> 90% of the activation of nuclear factor κB-like DNA binding activity in KS cells. PDTC also reduced by> 85% induced levels of VCAM-1 and IL-6 at the mRNA, protein, and functional levels in KS cells. In contrast, PDTC did not inhibit the induced expression of either ICAM-1 or E-selectin. These studies show that PDTC differentially modulates the expression of inflammatory response genes in KS cells that contain KSHV, suggesting that reduction-oxidation-sensitive events are involved in the regulation of these genes. These studies also suggest that thiol-antioxidants such as PDTC may play a potentially therapeutic role in the treatment of KS by preventing induction of specific inflammatory response genes that may be involved in the pathogenesis of KS.