Article ; Online: P2Y6 receptor-mediated signaling amplifies TLR-induced pro-inflammatory responses in microglia.
2022 Volume 13, Page(s) 967951
Abstract: TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the ... ...
Abstract | TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the microenvironment. Purinergic receptors are powerful modulators of TLR-induced responses, and we here characterized the effects of P2Y6 receptor (P2RY6)-mediated signaling on TLR responses of rhesus macaque primary bone marrow-derived macrophages (BMDM) and microglia, using the selective P2RY6 antagonist MRS2578. We demonstrate that P2RY6-mediated signaling enhances the levels of TLR-induced pro-inflammatory cytokines in microglia in particular. TLR1, 2, 4, 5 and 8-induced responses were all enhanced in microglia, whereas such effects were much less pronounced in BMDM from the same donors. Transcriptome analysis revealed that the overall contribution of P2RY6-mediated signaling to TLR-induced responses in microglia leads to an amplification of pro-inflammatory responses. Detailed target gene analysis predicts that P2RY6-mediated signaling regulates the expression of these genes |
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MeSH term(s) | Animals ; Cytokines/metabolism ; Heat-Shock Proteins/metabolism ; Macaca mulatta ; Microglia ; NF-kappa B/metabolism ; Receptors, Purinergic P2 ; Toll-Like Receptor 1/metabolism |
Chemical Substances | Cytokines ; Heat-Shock Proteins ; NF-kappa B ; Receptors, Purinergic P2 ; Toll-Like Receptor 1 ; purinoceptor P2Y6 |
Language | English |
Publishing date | 2022-09-20 |
Publishing country | Switzerland |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2606827-8 |
ISSN | 1664-3224 ; 1664-3224 |
ISSN (online) | 1664-3224 |
ISSN | 1664-3224 |
DOI | 10.3389/fimmu.2022.967951 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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