SIGNAL 1 ALONE IS ENOUGH TO ACTIVATE THE NLRP3 INFLAMMAOSME IN HUMAN CELLS According to our current understanding,the NLR family,pyrin domain containing 3(NLRP3)infl ammasome activation is generally a two-step process.The fi rst step is priming,in which pathogen associated molecular patterns(PAMPs)such as LPS or pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α)induced NF-κB activation provides synthesis of pro-IL-1βand NLRP3 proteins.This priming step is considered as signal 1,which makes the cell ready for a second strike to assemble the infl ammasome.Then danger signals such as ATP and MSU provide the signal 2 that promotes formation of the NLRP3 infl ammasome and activates caspase-1.Both of these 2 steps are required in mouse macrophages for the NLRP3 inflammasome activation(Dinarello,2007).
Pannexin-1(Panx1)forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation,ATP release and phagocytes recruitment.In the current study,by manipulation of Panx1 expression in human myeloid cells and application of Panx1 defi cient mice,we failed to fi nd a correlation between Panx1 and NLRP3 infl ammasome activation,although an interaction between these two proteins was evident.However,in thioglycollate induced peritonitis,Panx1 defi cient mice showed much more phagocytes infiltration.Further analyses showed that mice defi cient for Panx1 exhibited enlarged F4/80^(low)Gr1-Ly6C-cell population in the peritonea.Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.
