LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-γ, LPS and microbial infection
LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-γ, LPS and microbial infection
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DOI：
10.1007/s00251-005-0057-2
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发表时间：
2006-01-01
期刊：
影响因子：
3.2
通讯作者：
O'Gara, F
中科院分区：
文献类型：
--
作者：
Mulcahy, H;O'Rourke, KP;O'Gara, F
主要组织相容性复合体（MHC）中心区域的许多基因编码参与免疫和炎症反应的蛋白质。在这项研究中，我们进一步表征了MHC IV类区域的两个基因，白细胞特异性转录本（LST） 1和天然细胞毒性触发受体3 (NCR3)（也称为1C7和自然杀手（NK）p30）。LST1的具体功能尚不清楚，尽管表达分析和功能数据表明其具有免疫调节作用。LST1基因经历广泛的选择性剪接，产生膜结合（由外显子3编码）和可溶性同种异构体。NCR3蛋白参与NK介导的细胞毒性，并在NK/树突状细胞串扰中发挥作用。通过实时逆转录聚合酶链反应检测这些基因在自身免疫诱导炎症中的表达，特别是风湿性关节炎影响的血液和滑膜，以及对炎症介质和细菌药物刺激的反应。LST1的表达，特别是编码可溶性异构体和NCR3的剪接变异，在风湿性关节炎影响的血液和滑膜中增加，并与滑膜中更严重的炎症有关。此外，这两个基因在脂多糖、干扰素(IFN)- γ和细菌感染的反应中均显著上调。这些发现表明NCR3和LST1的可溶性亚型可能在炎症和感染性疾病中发挥作用。
Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase-polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-gamma and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.