【摘 要】
：
Aim Activation of cannabinoid receptor 2 (CB2R) has been reported to ameliorate the pathogenesis of experimental autoimmune encephalomyelitis (EAE).In this study, we examined whether autophagy is invo
【机 构】
：
Department of Pharmacology,Second Military Medical University,Shanghai 200433,China
论文部分内容阅读
Aim Activation of cannabinoid receptor 2 (CB2R) has been reported to ameliorate the pathogenesis of experimental autoimmune encephalomyelitis (EAE).In this study, we examined whether autophagy is involved in the beneficial effect of CB2R on EAE and explored the mechanism with a focus on inflammasome activation.Methods EAE severity was analyzed with clinical score and histological score stained by hematoxylin and eosin or luxol fast blue in spinal cord.Immunoblot analysis was conducted to detect proteins of NODlike receptor family, pyrin domain containing 3 (NLRP3) inflammasomerelated caspase1 (Casp1) and the maturation of interleukin (IL)1β as well as autophagyrelated light chain 3 (LC3) and Beciln 1 both in vivo and in vitro.Reverse transcription and realtime PCR were used to detect mRNA of NLRP3, IL1 β and Casp1.Autophagyrelated gene 5 (ATG5)specific siRNA was transiently transfected in BV2 microglia and immunofluorescence staining was carried out to detect the expression of NLRP3, caspase recruitment domain (ASC), and procaspase1.Results The current data indicated that deleting CB2R decreased the expression of LC3Ⅱ/LC3Ⅰ ratio, Beclin 1 and increased caspase1 activation and IL13 production in the spinal cord of EAE mice, whereas activation of CB2R with a specific agonist HU308 induced inverse effects.Further study indicated that HU308 could promote autophagy and inhibit expression and activation of NLRP3 inflammasome in BV2 microglia.Blocking autophagy by ATG5specific siRNA dismissed the effort of CB2R in mediating NLRP3 inflammasome in vitro.Conclusion Collectively, our results demonstrated for the first time that CB2R plays a protective role in EAE through promoting autophagy and inhibiting NLRP3 inflammasome activation.
其他文献
Our recent study demonstrated that pinocembrin (PB), the most abundant flavonoid in propolis, has neuroprotective effect against 1methyl4phenylpyridinium (MPP +)induced SHSY5Y neurotoxicity.However,th
Aim Posttraumatic nightmares are a core component of posttraumatic stress disorder (PTSD) and mechanistically linked to the development and maintenance of this disorder, but little is known about thei
Aim It has been widely accepted that autophagy plays a key role in some human diseases such as Parkinson s disease (PD).UNC5 llike kinasesl (ULK1) has been widely reported to initiate autophagy via it
Aim Fragile X mental retardation protein (FMRP) is an RNAbinding protein important for the control of translation and synaptic function.The mutation or silencing of FMRP causes Fragile X syndrome (FXS
Aim Leptin, a 16 ku hormone from the ob gene, has been identified as an important protein involved obesity.As a chronic metabolic disorder, Obesity is associated with a high risk of developing cardiov
Aim To investigate the effect of hydrogenrich saline on arterial thrombosis in sinoaortic denervatted(SAD) rats.Methods Rats were divided randomly into Sham group, SAD group, SAD + hydrogenrich saline
Aim Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cardiocerebrovascular physiopathological process.It is also a promising anticancer target.It is highly desirable to discov
This study aimed to explore the effect of DT13 (25(R,S)ruscogenin10βdglucopyranosyl(1→2)][βdxylopyranosyl(1→3)]βdfucopyranoside) on tumor necrosis factor (TNF)αinduced vascular inflammation and the po
Aim Aging is an independent risk factor for heart disease, however the effective intervention has not been found so far.Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide varie
Aim To evaluate the timeeffect and doseeffect of prasugrel hydrobromide acetic acid compound(PHAAC) inhibiting platelet aggregation.Methods For the timeeffect study, 190 SpragueDawley (SD) rats were d