中华微生物学和免疫学杂志
中華微生物學和免疫學雜誌
중화미생물학화면역학잡지
CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
2014年
5期
331-336
,共6页
张晓卿%孙燕%马茜%汪洋%路玲玲
張曉卿%孫燕%馬茜%汪洋%路玲玲
장효경%손연%마천%왕양%로령령
肿瘤免疫%细胞杀伤%JNK%NK细胞%NKG2D
腫瘤免疫%細胞殺傷%JNK%NK細胞%NKG2D
종류면역%세포살상%JNK%NK세포%NKG2D
Tumor immunity%Cell killing%c-Jun N-terminal kinase%Natural killer cell%NKG2D
目的:探讨c-Jun氨基末端激酶2(c-Jun N-terminal kinase,JNK2)信号通路对自然杀伤( NK)细胞肿瘤杀伤效应的影响。方法采用Western blot检测活化淋巴细胞中JNK信号及其上游激酶的磷酸化情况;采用体外杀伤试验和流式细胞技术检测JNK2缺失对NKG2D ( natural-killer group 2 member D)介导的NK细胞效应细胞因子产生及肿瘤杀伤的影响;利用JNK2基因敲除小鼠构建移植瘤模型,对其皮下肿瘤生长情况进行观察和检测,并与野生型小鼠进行比较。结果淋巴细胞早期活化伴随着JNK及其上游激酶的活化。肿瘤细胞表达的高亲和力NKG2D配体可显著增强NK细胞对肿瘤细胞的杀伤作用。当JNK2信号通路缺失后,经NKG2D介导的NK细胞效应细胞因子产生及肿瘤清除的能力均显著减弱,进而导致机体肿瘤控制能力减弱。结论 JNK2信号通路对由NKG2D 介导的NK细胞活化、NK细胞的肿瘤清除和免疫监视能力具有重要的调节作用。
目的:探討c-Jun氨基末耑激酶2(c-Jun N-terminal kinase,JNK2)信號通路對自然殺傷( NK)細胞腫瘤殺傷效應的影響。方法採用Western blot檢測活化淋巴細胞中JNK信號及其上遊激酶的燐痠化情況;採用體外殺傷試驗和流式細胞技術檢測JNK2缺失對NKG2D ( natural-killer group 2 member D)介導的NK細胞效應細胞因子產生及腫瘤殺傷的影響;利用JNK2基因敲除小鼠構建移植瘤模型,對其皮下腫瘤生長情況進行觀察和檢測,併與野生型小鼠進行比較。結果淋巴細胞早期活化伴隨著JNK及其上遊激酶的活化。腫瘤細胞錶達的高親和力NKG2D配體可顯著增彊NK細胞對腫瘤細胞的殺傷作用。噹JNK2信號通路缺失後,經NKG2D介導的NK細胞效應細胞因子產生及腫瘤清除的能力均顯著減弱,進而導緻機體腫瘤控製能力減弱。結論 JNK2信號通路對由NKG2D 介導的NK細胞活化、NK細胞的腫瘤清除和免疫鑑視能力具有重要的調節作用。
목적:탐토c-Jun안기말단격매2(c-Jun N-terminal kinase,JNK2)신호통로대자연살상( NK)세포종류살상효응적영향。방법채용Western blot검측활화림파세포중JNK신호급기상유격매적린산화정황;채용체외살상시험화류식세포기술검측JNK2결실대NKG2D ( natural-killer group 2 member D)개도적NK세포효응세포인자산생급종류살상적영향;이용JNK2기인고제소서구건이식류모형,대기피하종류생장정황진행관찰화검측,병여야생형소서진행비교。결과림파세포조기활화반수착JNK급기상유격매적활화。종류세포표체적고친화력NKG2D배체가현저증강NK세포대종류세포적살상작용。당JNK2신호통로결실후,경NKG2D개도적NK세포효응세포인자산생급종류청제적능력균현저감약,진이도치궤체종류공제능력감약。결론 JNK2신호통로대유NKG2D 개도적NK세포활화、NK세포적종류청제화면역감시능력구유중요적조절작용。
Objective To investigate the effects of c-Jun N-terminal kinase (JNK) 2 on NKG2D-mediated natural killer ( NK) cell cytotoxicity .Me thods NK cells were activated by polyinosinic-polycyti-dylic acid ( Poly I∶C ) .The activation status of JNK signaling pathway was detected .The cytotoxicity of ac-tivated NK cells and the level of IFN-γproduced were measured to determine the function of NK cells in the absence of JNK2.Tumor growth in wild type and JNK2-knockout (JNK2-/-) mice with lymphoma xenograft were measured to evaluate immune surveillance of NK cells .Results The phosphorylation of JNK and up-stream kinases were observed in the early stage of cell activation after treatment of Poly I ∶C.The expressed ligands of the activating receptors NKG2 D significantly increased NK cell cytotoxicity to lymphoma cells . JNK2 deficiency impaired the antitumor effects of NK cells , and then resulted in enhanced tumor growth in JNK2-/-mice.Conclusion JNK2 signaling pathway is involved in the NKG2 D-mediated activation of NK cells and regulates immune surveillance of NK cells against tumor .