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NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β-Estradiol
Joint Authors
Vadlamudi, Ratna K.
Thakkar, Roshni
Wang, Ruimin
Sareddy, Gangadhara
Wang, Jing
Thiruvaiyaru, Dharma
Zhang, Quanguang
Brann, Darrell
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-10-23
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
17β-Estradiol (E2) is a well-known neuroprotective factor in the brain.
Recently, our lab demonstrated that the neuroprotective and cognitive effects of E2 require mediation by the estrogen receptor (ER) coregulator protein and proline-, glutamic acid-, and leucine-rich protein 1 (PELP1).
In the current study, we examined whether E2, acting via PELP1, can exert anti-inflammatory effects in the ovariectomized rat and mouse hippocampus to regulate NLRP3 inflammasome activation after global cerebral ischemia (GCI).
Activation of the NLRP3 inflammasome pathway and expression of its downstream products, cleaved caspase-1 and IL-1β, were robustly increased in the hippocampus after GCI, with peak levels observed at 6-7 days.
Expression of P2X7 receptor, an upstream regulator of NLRP3, was also increased after GCI.
E2 markedly inhibited NLRP3 inflammasome pathway activation, caspase-1, and proinflammatory cytokine production, as well as P2X7 receptor expression after GCI (at both the mRNA and protein level).
Intriguingly, the ability of E2 to exert these anti-inflammatory effects was lost in PELP1 forebrain-specific knockout mice, indicating a key role for PELP1 in E2 anti-inflammatory signaling.
Collectively, our study demonstrates that NLRP3 inflammasome activation and proinflammatory cytokine production are markedly increased in the hippocampus after GCI, and that E2 signaling via PELP1 can profoundly inhibit these proinflammatory effects.
American Psychological Association (APA)
Thakkar, Roshni& Wang, Ruimin& Sareddy, Gangadhara& Wang, Jing& Thiruvaiyaru, Dharma& Vadlamudi, Ratna K.…[et al.]. 2016. NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β-Estradiol. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1114319
Modern Language Association (MLA)
Thakkar, Roshni…[et al.]. NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β-Estradiol. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-17.
https://search.emarefa.net/detail/BIM-1114319
American Medical Association (AMA)
Thakkar, Roshni& Wang, Ruimin& Sareddy, Gangadhara& Wang, Jing& Thiruvaiyaru, Dharma& Vadlamudi, Ratna K.…[et al.]. NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β-Estradiol. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1114319
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1114319