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强毒力牛分枝杆菌北京株激活THP-1巨噬细胞中的NLRP7炎性小体。

Virulent Mycobacterium bovis Beijing Strain Activates the NLRP7 Inflammasome in THP-1 Macrophages.

作者信息

Zhou Yang, Shah Syed Zahid Ali, Yang Lifeng, Zhang Zhongqiu, Zhou Xiangmei, Zhao Deming

机构信息

National Animal Transmissible Spongiform Encephalopathy Laboratory, Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.

Veterinary Bureau, Ministry of Agriculture of the People's Republic of China, Beijing 100125, China.

出版信息

PLoS One. 2016 Apr 4;11(4):e0152853. doi: 10.1371/journal.pone.0152853. eCollection 2016.

Abstract

Mycobacterium bovis is the causative agent of tuberculosis in a wide range of mammals, including humans. Macrophages are the first line of host defense. They secrete proinflammatory cytokines, such as interleukin-1 beta (IL-1β), in response to mycobacterial infection, but the underlying mechanisms by which human macrophages are activated and release IL-1β following M. bovis infection are poorly understood. Here we show that the 'nucleotide binding and oligomerization of domain-like receptor (NLR) family pyrin domain containing 7 protein' (NLRP7) inflammasome is involved in IL-1β secretion and caspase-1 activation induced by M. bovis infection in THP-1 macrophages. NLRP7 inflammasome activation promotes the induction of pyroptosis as well as the expression of tumor necrosis factor alpha (TNF-α), Chemokine (C-C motif) ligand 3 (CCL3) and IL-1β mRNAs. Thus, the NLRP7 inflammasome contributes to IL-1β secretion and induction of pyroptosis in response to M. bovis infection in THP-1 macrophages.

摘要

牛分枝杆菌是包括人类在内的多种哺乳动物结核病的病原体。巨噬细胞是宿主防御的第一道防线。它们在受到分枝杆菌感染时会分泌促炎细胞因子,如白细胞介素-1β(IL-1β),但人们对牛分枝杆菌感染后人类巨噬细胞被激活并释放IL-1β的潜在机制了解甚少。在这里,我们表明“含吡啉结构域的核苷酸结合寡聚化结构域样受体(NLR)家族7蛋白”(NLRP7)炎性小体参与了牛分枝杆菌感染THP-1巨噬细胞诱导的IL-1β分泌和半胱天冬酶-1激活。NLRP7炎性小体激活促进细胞焦亡的诱导以及肿瘤坏死因子α(TNF-α)、趋化因子(C-C基序)配体3(CCL3)和IL-1β mRNA的表达。因此,NLRP7炎性小体有助于THP-1巨噬细胞在牛分枝杆菌感染时分泌IL-1β并诱导细胞焦亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e0/4820140/3998617044de/pone.0152853.g001.jpg

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