Dexmedetomidine inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades

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dc.contributor.authorLi, Hu
dc.contributor.authorZhang, Xueping
dc.contributor.authorChen, Mingfu
dc.contributor.authorChen, Jianyan
dc.contributor.authorGao, Tao
dc.contributor.authorYao, Shanglong
dc.date.accessioned2018-07-06T07:37:26Z
dc.date.available2018-07-06T07:37:26Z
dc.date.issued2018-03-22
dc.description.abstractNOD-like receptor 3 (NLRP3) plays critical roles in the initiation of inflammasome-mediated inflammation in microglia, thus becomes an important therapeutic target of Alzheimer’s disease (AD). Dexmedetomidine (Dex), a new type of clinical anesthetic agent, shows anti-inflammatory properties and inhibits postoperative cognitive dysfunction in AD patients. The present study was aimed to investigate effect of Dex on NLRP3 activity in activated microglia and reveal the underlying mechanisms. The human microglia clone 3 (HMC3) cells were exposed to 100 ng/ml LPS and 5 mM ATP, in the presence and absence of doses of Dex. Data from ELISA and Western blot assays showed that Dex abrogated the promoting effects of LPS/ATP on the release of pro-inflammatory cytokines including IL-1ß and IL-18 in the cell medium and the expression of NLRP3 and its downstream target caspase-1 in HMC3 cells. Furthermore, the present study found that exposure of HMC3 cells to LPS/ATP increased nuclear protein levels of transcription factor c-Fos, but treatment with Dex reversed the increase in c-Fos, as indicated by Western blot and immunofluorescence measures. Luciferase reported assay revealed that c-Fos can bind to the promoter region of NLRP3 gene and positively regulate the expression. These results suggest that Dex inhibiting c-Fos nuclear protein levels promoted by LPS/ATP blocks the up-regulation of NLRP3. This suggestion is supported by co-immunoprecipitation and PCR studies, in which Dex decreased the amount of c-Fos that binds to NLRP3 under the stimulation of LPS/ATP. The present study revealed that Dex inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades, which adds new understanding of the anti-inflammatory mechanism of Dex.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/36964
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-18963
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 17 2018
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDexmedetomidineen
dc.subjectNLRP3en
dc.subjectInflammatoryen
dc.subjectMicrogliaen
dc.subject.ddc610
dc.titleDexmedetomidine inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascadesen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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