miR-34a inhibits BCL-2 activation of the NLRP1 inflammasomeinduced epilepsy in mice

Objective:To explore the related mechanism of miR-34a affecting epilepsy.Methods:MicroRNA microarray chip and RT-PCR were used to analyze the expression of miR-34a in epileptic rats,and observe the relationship between miR-34a and seizure frequency and EEG.Predicted the target gene of miR-34a,used The dual-luciferase reporter gene assay was used to observe its binding to the target gene of miR-34a,the effect of overexpression and inhibition of miR-34a on the target gene,the effects of overexpression and inhibition of target genes on downstream factors.Results:Microarray chip and RT-PCR detection showed that miR-34a was highly expressed in epilepsy(P<0.05),and miR-34a was positively correlated with seizure frequency(R=0.783,P=0.003),and inhibition of miR-34a inhibited the seizure frequency of epilepsy(P<0.05).The online databases TargetScan and miRDB show that miR-34a and BCL-2 have a predicted binding region,and the dual-luciferase reporter gene experiment proves that the two have a binding relationship.When miR-34a was overexpressed,BCL-2 expression was down-regulated,and conversely,when miR-34a was inhibited,BCL-2 expression was up-regulated.NLRP1 and downstream related factors Caspase-3,Caspase-1,IL-1βand IL-18 were highly expressed in the brain tissue of epileptic rats(P<0.05).When BCL-2 was inhibited,the expression levels of NLRP1 and downstream related factors were increased,and when BCL-2 was inhibited,the result was the opposite.Conclusion:The highly expressed miR-34a promotes epilepsy by inhibiting BCL-2 and activating the NLRP1 inflammasome.

Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages

Streptococcus mutans(S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin(IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma(AIM2), NLR family pyrin domain-containing 3(NLRP3) and NLR family CARD domain-containing 4(NLRC4)inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate(ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.