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. 2019 Feb 27;10:141. doi: 10.3389/fphys.2019.00141

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Copyright © 2019 Zhou, Green, Bennet, Gunn and Davidson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic diagram of the potential involvement of connexin 43 hemichannels and pannexin 1 channels and purinergic receptors P2X4 and P2X7 in the activation of microglia and NLRP3 inflammasome. Cx43 hemichannels and Px1 channels may open after exposure to HI or infection/inflammation. The opening of these channels leads to the release of ATP into the extracellular space. Extracellular ATP can activate purinergic receptors P2X4R and P2X7R. The activation of P2X4R and P2X7R can lead to the activation of microglia. Signal 1 of NLRP3 inflammasome activation is provided by PAMPs or DAMPs, which leads to the upregulation of NLRP3, pro-IL-1β, and pro-IL-18. Signal 2 is mediated by ATP activation of P2X7R and can lead to the assembly of NLRP3, ASC, and pro-caspase 1, forming the NLRP3 inflammasome. Pro-caspase 1 is activated into caspase 1, which cleaves pro-IL-1β and pro-IL-18 into their mature forms. Mature IL-1β and IL-18 is secreted.