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Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions

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Abstract

The nucleotide receptor P2X7 is an attractive therapeutic target and potential biomarker for multiple inflammatory and neurologic disorders, and it is expressed in several immune, osteogenic, and neurologic cell types. Aside from its role in the nervous system, it is activated by ATP released at sites of tissue damage, inflammation, and infection. Ligand binding to P2X7 stimulates many cell responses, including calcium fluxes, MAPK activation, inflammatory mediator release, and apoptosis. Much work has centered on P2X7 action in cell death and mediator processing (e.g., pro-interleukin-1 cleavage by the inflammasome), but the contribution of P2X7 to transcriptional regulation is less well defined. This review will focus on the growing evidence for the importance of nucleotide-mediated gene expression, highlight several animal models, human genetic, and clinical studies that support P2X7 as a therapeutic target, and discuss the latest developments in anti-P2X7 clinical trials.

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Acknowledgments

This work was supported by National Institutes of Health (NIH) grants 1 U19 AI070503, 2 R01 HL069116, 5 R01 CA108467, and 1 P01 HL0885940 to PJB.

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Lenertz, L.Y., Gavala, M.L., Zhu, Y. et al. Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions. Immunol Res 50, 22–38 (2011). https://doi.org/10.1007/s12026-011-8203-4

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