PLUNC蛋白家族在抑制鼻咽上皮“炎．癌”演进中的作用和机制  

The Effect and Mechanism of PLUNC Protein Family Against Inflammation and Carcinogenesis of Nasopharyngeal Carcinoma

作　　者：魏芳[1,2] 李夏雨[1,2] 李小玲[1,2] 张文玲[2] 廖前进[2,3] 曾勇[3] 龚朝建[2] 周鸣[1,2] 马健[1,2] 熊炜[1,2] 沈守荣[1] 曾朝阳[1,2] 

机构地区：[1]中南大学湘雅三医院疾病基因组研究中心,非可控性炎症与肿瘤湖南省重点实验室,长沙410013 [2]中南大学肿瘤研究所,卫生部癌变原理重点实验室及教育部癌变与侵袭原理重点实验室,长沙410078 [3]中南大学湘雅医学院附属肿瘤医院,湖南省肿瘤医院,长沙410013

出　　处：《生物化学与生物物理进展》2014年第1期24-31,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81071644,81172189,81171930,81201730,81272298,81372907,81301757);湖南省自然科学基金(14JJ1010);中央高校基本科研业务费专项资金(2011JQ020)资助项目~~

摘　　要：人类鼻咽黏膜表面的分泌物中富含天然免疫蛋白,腭、肺及鼻咽上皮克隆(palate,lung and nasal epithelium clone,PLUNC)蛋白家族成员SPLUNC1和LPLUNC1就是其中的重要组成部分,这两个蛋白在鼻咽上皮相对特异高表达,它们都具有杀菌/渗透增强蛋白(bactericidal/permeability-increasing protein,BPI)结构域,可通过BPI结构域与细菌脂多糖(lipopolysaccharides,LPS)结合从而直接杀灭或抑制细菌生长,也可以有效抑制EB病毒(Epstein-Barr virus,EBV)等致癌微生物对鼻咽上皮的侵袭从而发挥其免疫防御功能.它们还可以通过抑制IL-6等炎症因子的分泌和NF-κB、STAT3等炎症相关通路的激活,阻止鼻咽部的慢性炎症反应及鼻咽上皮的恶性转化.在鼻咽癌细胞中重新表达PLUNC蛋白,可以通过促分裂素原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)或miR-141-PTEN-AKT等信号通路抑制鼻咽癌细胞的增殖,促进鼻咽癌细胞的凋亡.进一步深入研究PLUNC蛋白家族在鼻咽癌发病中的作用机制,对指导鼻咽癌的防治具有重要的意义.Secretion on the surface of human nasal mucosa contains many innate proteins, the key factors of which are SPLUNC1 and LPLUNC1, members of the palate, lung and nasal epithelium clone （PLUNC） family. These two proteins are highly expressed in nasopharyngeal epithelium with the relative specificity. Both of them have bacterial/permeability-increasing protein （BPI） domain which can bind to lipopolysaccharide （LPS） to inhibit or kill bacterial growth directly. They also have the immuno defense function to protect nasopharyngeal epithelium from Epstein-Barr virus （EBV） and some other pathogenic microorganism effectively. These proteins play a significant role in the process of chronic inflammation and carcinogenesis of nasopharyngeal epithelium by inhibiting the secretion of inflammatory factors, such as IL-6, through activating NF-KB and STAT3 signaling pathways. In addition, they also can suppress nasopharyngeal carcinoma （NPC） cell growth and induce cell apoptosis through MAPK and miR-141-PTEN-AKT signaling pathways when the PLUNC proteins are re-expressed in NPC cell lines. Further study about the mechanism of PLUNC protein family in pathogenesis of NPC has important significance for the prevention and treatment guidance of NPC.

关 键 词：PLUNC蛋白家族 炎症 鼻咽癌 

分 类 号：Q78[生物学—分子生物学]