title: Inflammasomes-dependent regulation of IL-1β secretion induced by the virulent Mycobacterium bovis Beijing strain in THP-1 macrophages.
abstract: Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection of macrophages with M. bovis leads to the activation of the "nucleotide binding and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3" (NLRP3) and "absent in melanoma 2" (AIM2) inflammasomes, which in turn triggers release of the proinflammatory cytokine interleukin-1β (IL-1β) that contributes to bacterial clearance and plays a crucial role in the host defense. However, NLRP3 and AIM2 inflammasome activation is influenced by several factors and how IL-1β secretion by M. bovis-infected macrophages is regulated via the inflammasome pathway remains unclear. Here we found that IL-1β secretion and pro-IL-1β protein accumulation were inhibited in THP-1 macrophages upon exposure to the virulent M. bovis Beijing strain in the presence of high K(+) concentrations, cycloheximide (a protein synthesis inhibitor) and PR-619 (a deubiquitinating enzyme inhibitor). Scavenging reactive oxygen species (ROS) induced by N-acetylcysteine reduced IL-1β release independent of the mitochondrial permeability transition. Collectively, our results suggest that IL-1β secretion by M. bovis-infected THP-1 macrophages is reduced by high extracellular K(+) concentration, inhibition of new protein synthesis, deubiquitination, and ROS generation.
authors.affiliation: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
authors.forename: Ruichao
authors.initials: R
authors.lastname: Yue
authors.forename: Sher Hayat
authors.initials: SH
authors.lastname: Khan
authors.forename: Syed Zahid Ali
authors.initials: SZ
authors.lastname: Shah
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D003513:Cycloheximide / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000276:immunology*; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D003513:Cycloheximide; D011188:Potassium