Human NLRP2 blocking peptide

Neuro-inflammation and neuronal communication are considered as mis-regulated processes in the aetiology and pathology of bipolar disorder (BD). Which and when specific signal pathways become abnormal during the ontogeny of bipolar disorder patients is unknown. To address this question, we applied induced pluripotent stem cell (iPSC) technology followed by cortical neural differentiation on adipocyte-derived cells from BD type I patients (with psychotic episodes in psychiatric history) and healthy volunteers (controls). RNA sequencing in iPSC and cortical neural stem cell (NSC) lines were used to examine alterations between the transcriptomes from BD I and control samples during transition from the pluripotent stage towards the neural developmental stage. At the iPSC stage, the most highly significant differentially expressed gene (DEG) was the NLRP2 inflammasome (P = 2.66 x 10(-10)). Also among 42 DEGs at the NSC stage, NLRP2 showed the strongest statistical significance (P = 3.07 x 10(-19)). In addition, we have also identified several cytoskeleton-associated genes as DEGs from the NSC stage, such as TMP2, TAGLN and ACTA2; the former two genes are recognised for the first time to be associated with BD. Our results also suggest that iPSC-derived BD-cortical NSCs carry several abnormalities in dopamine and GABA receptor canonical pathways, underlining that our in vitro BD model reflects pathology in the central nervous system. This would indicate that mis-regulated gene expression of inflammatory, neurotransmitter and cytoskeletal signalling occurs during early fetal brain development of BD I patients.

Periodontal disease is an inflammatory condition that destroys the tooth-supporting tissues. The inflammation is initiated by oral bacteria in the form of multi-species biofilms, and is dominated by cytokines of the IL-1 family. IL-1 activation and processing is regulated by Caspase-1, within intracellular protein complexes, known as "inflammasomes". The present study employed culture supernatants of in vitro supragingival and subgingival biofilms, to challenge human GF cultures for 6 h. The gene expression of inflammasome complex components was investigated by TaqMan qPCR. NLRP1 expression was not affected, whereas NLRP2 was not expressed. SupragingiVal biofilm challenge increased the expression of Caspase-1, the adaptor ASC, AIM2, as well as IL-1 beta and IL-18, but did not affect NLRP3 expression. Subgingival biofilm challenge enhanced Caspase-1, ASC, AIM2, IL-1 beta and IL-18 gene expression at lower concentrations, followed by their down-regulation at higher concentrations, which was also evident for NLRP3 expression. Hence, supragingival and subgingival biofilms differentially regulate the gene expressions of NLRP3 and AIM2 inflammasomes and their down-stream IL-1 targets. Increased inflammasome transcription in response to supragingival biofilms is commensurate with early inflammatory events in periodontal disease, whereas decreased transcription in response to subgingival biofilms corroborates the dampening of host immune responses, in favour of pathogen survival and persistence. (C) 2011 Elsevier Inc. All rights reserved.