Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor.
Adenosine Diphosphate
/ metabolism
Animals
Caspase 1
/ metabolism
Cell Line
Cytokines
/ metabolism
Gene Expression Regulation
/ physiology
Inflammasomes
/ metabolism
Inflammation
/ metabolism
Inflammation Mediators
/ metabolism
Interleukin-1beta
/ metabolism
Macrophages
/ metabolism
Mice
NF-kappa B
/ metabolism
Reactive Oxygen Species
/ metabolism
Receptors, Purinergic P2Y12
/ metabolism
Signal Transduction
/ physiology
IL-1β
NF-κB
NLRP3 inflammasome
P2Y12 receptor
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
18
11
2018
revised:
31
07
2019
accepted:
23
09
2019
pubmed:
25
9
2019
medline:
14
7
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
The NLRP3 inflammasome is a molecular complex that translates signals from pathogens and tissue damage into inflammatory responses, and plays crucial roles in numerous neurological diseases. Activation of the NLRP3 inflammasome leads to caspase-1 dependent cleavage of pro-IL-1β to form mature IL-1β. By acting on the P2X7 purinergic receptor, extracellular ATP is one of the major stimuli that activates the NLRP3 inflammasome. Although microglia express multiple purinergic receptors, their roles in inflammasome-mediated inflammation are largely unknown. We studied the role of the P2Y12 receptor, a metabotropic P2Y receptor enriched in microglia, on inflammation in vitro. Inhibition of the microglial P2Y12 receptor by PSB0739 or siRNA knockdown suppressed IL-1β release. P2Y12 receptor-deficient microglia displayed markedly attenuated IL-1β mRNA expression and release. P2Y12 receptor blockade also suppressed IL-6 production. Both IL-1β and IL-6 responses were augmented by extracellular ADP or ADP-βS and were abrogated by PSB0739. Mechanistically, ADP-βS potentiated NF-κB activation. In addition, ADP altered mitochondrial membrane potential in combination with ATP and increased the number of caspase-1 positive cells through the P2Y12 receptor. These results elucidate a novel inflammatory mechanism by which extracellular ADP acts on the P2Y12 receptor to activate NF-κB and the NLRP3 inflammasome to enhance microglial inflammation.
Identifiants
pubmed: 31549730
doi: 10.1002/eji.201848013
doi:
Substances chimiques
Cytokines
0
Inflammasomes
0
Inflammation Mediators
0
Interleukin-1beta
0
NF-kappa B
0
P2ry12 protein, mouse
0
Reactive Oxygen Species
0
Receptors, Purinergic P2Y12
0
Adenosine Diphosphate
61D2G4IYVH
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
205-219Subventions
Organisme : JSPS KAKENHI
ID : 26461556
Pays : International
Organisme : Japan Society for the Promotion of Science
ID : 26461556
Pays : International
Organisme : Japan Society for the Promotion of Science
ID : HS
Pays : International
Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
Shichita, T., Sakaguchi, R., Suzuki, M. and Yoshimura, A., Post-ischemic inflammation in the brain. Front. Immunol. 2012. 3: 132.
Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H. et al., Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015. 14: 388-405.
Vezzani, A., French, J., Bartfai, T. and Baram, T. Z., The role of inflammation in epilepsy. Nat. Rev. Neurol. 2011. 7: 31-40.
Gendelman, H. E., Neural immunity: friend or foe? J. Neurovirol. 2002. 8: 474-479.
Grace, Y. Chen and Gabriel, N., Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 2010. 12: 826-837.
Kono, H. and Rock, K. L., How dying cells alert the immune system to danger. Nat. Rev. Immunol. 2008. 8: 279-289.
Koizumi, S., Ohsawa, K., Inoue, K. and Kohsaka, S., Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors. Glia 2013. 61: 47-54.
Imura, Y., Morizawa, Y., Komatsu, R., Shibata, K., Shinozaki, Y., Kasai, H., Moriishi, K. et al., Microglia release ATP by exocytosis. Glia 2013. 61: 1320-1330.
Idzko, M., Ferrari, D. and Eltzschig, H. K., Nucleotide signalling during inflammation. Nature 2014. 509: 310-317.
Junger, W. G., Immune cell regulation by autocrine purinergic signalling. Nat. Rev. Immunol. 2011. 11: 201-212.
Latz, E., Xiao, T. S. and Stutz, A., Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 2013. 13: 397-411.
Bergsbaken, T., Fink, S. L. and Cookson, B. T., Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 2009. 7: 99-109.
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A. et al., NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013. 493: 674-678.
Vezzani, A., Maroso, M., Balosso, S., Sanchez, M. A. and Bartfai, T., IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav. Immun. 2011. 25: 1281-1289.
Guo, H., Callaway, J. B. and Ting, J. P., Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 2015. 21: 677-687.
Madry, C., Arancibia-Carcamo, I. L., Kyrargyri, V., Chan, V. T. T., Hamilton, N. B. and Attwell, D., Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion. Proc. Natl. Acad. Sci. U. S. A. 2018. 115: E1608-E1617.
Gicquel, T., Victoni, T., Fautrel, A., Robert, S., Gleonnec, F., Guezingar, M., Couillin, I. et al., Involvement of purinergic receptors and NOD-like receptor-family protein 3-inflammasome pathway in the adenosine triphosphate-induced cytokine release from macrophages. Clin. Exp. Pharmacol. Physiol. 2014. 41: 279-286.
Ben Addi, A., Cammarata, D., Conley, P. B., Boeynaems, J. M. and Robaye, B., Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP. J. Immunol. 2010. 185: 5900-5906.
Munoz-Planillo, R., Kuffa, P., Martinez-Colon, G., Smith, B. L., Rajendiran, T. M. and Nunez, G., K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 2013. 38: 1142-1153.
Zhou, R., Yazdi, A. S., Menu, P. and Tschopp, J., A role for mitochondria in NLRP3 inflammasome activation. Nature 2011. 469: 221-225.
Cottet-Rousselle, C., Ronot, X., Leverve, X. and Mayol, J. F., Cytometric assessment of mitochondria using fluorescent probes. Cytometry A 2011. 79: 405-425.
Jacobson, K. A., Balasubramanian, R., Deflorian, F. and Gao, Z. G., G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal. 2012. 8: 419-436.
von Kugelgen, I. and Hoffmann, K., Pharmacology and structure of P2Y receptors. Neuropharmacology 2016. 104: 50-61.
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V. et al., UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 2007. 446: 1091-1095.
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W. B. and Julius, D., The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 2006. 9: 1512-1519.
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T. et al., Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 2014. 17: 131-143.
Eyo, U. B., Peng, J., Swiatkowski, P., Mukherjee, A., Bispo, A. and Wu, L. J., Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. J. Neurosci. 2014. 34: 10528-10540.
Sipe, G. O., Lowery, R. L., Tremblay, M. E., Kelly, E. A., Lamantia, C. E. and Majewska, A. K., Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex. Nat. Commun. 2016. 7: 10905.
Charolidi, N., Schilling, T. and Eder, C., Microglial Kv1.3 channels and P2Y12 receptors differentially regulate cytokine and chemokine release from brain slices of young adult and aged mice. PLoS One 2015. 10: e0128463.
Moore, C. S., Ase, A. R., Kinsara, A., Rao, V. T., Michell-Robinson, M., Leong, S. Y., Butovsky, O. et al., P2Y12 expression and function in alternatively activated human microglia. Neurol. Neuroimmunol. Neuroinflamm. 2015. 2: e80.
Madry, C., Kyrargyri, V., Arancibia-Carcamo, I. L., Jolivet, R., Kohsaka, S., Bryan, R. M. and Attwell, D., Microglial ramification, surveillance, and interleukin-1beta release are regulated by the two-pore domain K(+) channel THIK-1. Neuron 2018. 97: 299-312 e296.
Di, A., Xiong, S., Ye, Z., Malireddi, R. K. S., Kometani, S., Zhong, M., Mittal, M. et al., The TWIK2 potassium efflux channel in macrophages mediates NLRP3 inflammasome-induced inflammation. Immunity 2018. 49: 56-65 e54.
Corriden, R. and Insel, P. A., Basal release of ATP: an autocrine-paracrine mechanism for cell regulation. Sci. Signal. 2010. 3: re1.
Sakaki, H., Tsukimoto, M., Harada, H., Moriyama, Y. and Kojima, S., Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor. PLoS One 2013. 8: e59778.
Swiatkowski, P., Murugan, M., Eyo, U. B., Wang, Y., Rangaraju, S., Oh, S. B. and Wu, L. J., Activation of microglial P2Y12 receptor is required for outward potassium currents in response to neuronal injury. Neuroscience 2016. 318: 22-33.
Cullen, S. P., Kearney, C. J., Clancy, D. M. and Martin, S. J., Diverse Activators of the NLRP3 inflammasome promote IL-1beta secretion by triggering necrosis. Cell Rep. 2015. 11: 1535-1548.
Bohlen, C. J., Bennett, F. C., Tucker, A. F., Collins, H. Y., Mulinyawe, S. B. and Barres, B. A., Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron 2017. 94: 759-773 e758.
Funk, K. E. and Klein, R. S., CSF1R antagonism limits local restimulation of antiviral CD8(+) T cells during viral encephalitis. J. Neuroinflamm. 2019. 16: 22.
Cossarizza, A., Chang, H. D., Radbruch, A., Acs, A., Adam, A., Adam-Klages, S., Agace, W. et al., Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 2019. 49: 1457-1973.