The MAPK family member JNK/stress-activated MAPK (SAPK) is involved in extracellular stress and proinflammatory cytokine responses, including production of cytokines such as IL-12. The JNK1 and 2 isoforms are widely expressed, but JNK3 is largely restricted to tissues of the brain, testis, and heart. In this study, we focus on mouse neutrophils, a cell type in which JNK/SAPK expression and activity has been given little study. We used Western blot analysis to examine expression patterns of JNK/SAPK in wild-type and JNK2-/- polymorphonuclear leukocytes (PMN). Surprisingly, neutrophils displayed a major deficiency in JNK1 expression, in contrast to macrophages that expressed high levels of both JNK1 and JNK2 MAPK. JNK1 expression was steadily reduced during the neutrophil maturation in bone marrow. We used PMN infection with the protozoan parasite Toxoplasma gondii to determine whether neutrophil JNK2 was functional. The parasite induced rapid JNK2 phosphorylation and intracellular FACS staining demonstrated preferential activation in infected neutrophils. Use of JNK2-/- neutrophils revealed that this MAPK family member was required for PMN IL-12p40 and CCL2/MCP-1 production. The chemotactic response displayed a minor JNK2 dependence but phagocytosis and oxidative burst activity did not require this MAPK. These findings are important because they demonstrate 1) a previously unrecognized unusual JNK expression pattern in mouse neutrophils, 2) JNK2 in PMN is activated by Toxoplasma invasion, and 3) a requirement for JNK2 in PMN IL-12p40 and CCL2/MCP-1 production in response to a microbial pathogen.

译文

MAPK家族成员JNK /应激激活MAPK(SAPK)与细胞外应激和促炎性细胞因子反应有关,包括细胞因子如IL-12的产生。 JNK1和2亚型广泛表达,但JNK3在很大程度上限于大脑,睾丸和心脏的组织。在这项研究中,我们集中于小鼠嗜中性粒细胞,这是一种细胞类型,其中对JNK / SAPK表达和活性的研究很少。我们使用蛋白质印迹分析来检查JNK / SAPK在野生型和JNK2-/-多形核白细胞(PMN)中的表达模式。出乎意料的是,嗜中性粒细胞在JNK1表达中表现出主要缺陷,这与表达高水平JNK1和JNK2 MAPK的巨噬细胞相反。在骨髓中性粒细胞成熟过程中,JNK1表达稳定降低。我们使用原生动物寄生虫弓形虫PMN感染来确定中性粒细胞JNK2是否起作用。寄生虫诱导的快速JNK2磷酸化和细胞内FACS染色显示在感染的中性粒细胞中优先激活。使用JNK2-/-中性粒细胞表明该MAPK家族成员是PMN IL-12p40和CCL2 / MCP-1生产所必需的。趋化反应显示出较小的JNK2依赖性,但吞噬作用和氧化爆发活性不需要此MAPK。这些发现很重要,因为它们证明了1)小鼠嗜中性粒细胞中以前无法识别的异常JNK表达模式,2)PMN中的JNK2被弓形虫入侵激活,3)PMN IL-12p40和CCL2 / MCP-1生产中对JNK2的要求对微生物病原体的反应。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录