Unknown

Dataset Information

0

Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates.


ABSTRACT: In acute inflammation, extracellular ATP activates P2X(7) ion channel receptors (P2X(7)R) on M1 polarized macrophages to release pro-inflammatory IL-1beta through activation of the caspase-1/nucleotide-binding domain and leucine-rich repeat receptor containing pyrin domain 3 (NLRP3) inflammasome. In contrast, M2 polarized macrophages are critical to the resolution of inflammation but neither actions of P2X(7)R on these macrophages nor mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes are known. Here, we investigated extracellular ATP signalling over a dynamic macrophage polarity gradient from M1 through M2 phenotypes. In macrophages polarized towards, but not at, M2 phenotype, in which intracellular IL-1beta remains high and the inflammasome is intact, P2X(7)R activation selectively uncouples to the NLRP3-inflammasome activation but not to upstream ion channel activation. In these intermediate M1/M2 polarized macrophages, extracellular ATP now acts through its pyrophosphate chains, independently of other purine receptors, to inhibit IL-1beta release by other stimuli through two independent mechanisms: inhibition of ROS production and trapping of the inflammasome complex through intracellular clustering of actin filaments.

SUBMITTER: Pelegrin P 

PROVIDER: S-EPMC2699392 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3964683 | biostudies-literature
| S-EPMC2556346 | biostudies-literature
| S-EPMC7360975 | biostudies-literature
2019-12-10 | MSV000084672 | MassIVE
| S-EPMC6882204 | biostudies-literature
| S-EPMC7214697 | biostudies-literature
| S-EPMC3058966 | biostudies-literature
| S-EPMC1221534 | biostudies-other
| S-EPMC4605898 | biostudies-literature
| S-EPMC175090 | biostudies-other