ArticlePediatric surgery international2019
Altered expression of inflammasomes in Hirschsprung's disease.
Article in Pediatric surgery international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Article
- Children with Hirschsprung disease exhibited alterations in host-microbial co-metabolism after pull-through operation.Pediatric surgery international · 2024Article
- Update on the Pathogenesis of the Hirschsprung-Associated Enterocolitis.International journal of molecular sciences · 2023Review
- A successful centre for translational paediatric surgical research.Pediatric surgery international · 2022Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim of the studyThe pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is poorly understood. Inflammasomes are a large family of multiprotein complexes that act to mediate host immune responses to microbial infection and have a regulatory or conditioning influence on the composition of the microbiota. Inflammasomes and the apoptosis-associated speck-like protein (ASC) lead to caspase-1 activation. The activated caspase-1 promotes secretion of pro-inflammatory cytokines (IL-1β and IL-18) from their precursors (pro-IL-1β and pro-IL-18). Inflammasomes have been implicated in a host of inflammatory disorders. Among the inflammasomes, NLRP3, NLRP12 and NLRC4 are the most widely investigated. Knock-out mice models of inflammasomes NLRP3, NLRP12, NLRC4, caspase-1 and ASC are reported to have higher susceptibility to experimental colitis. The purpose of this study was to investigate the expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1β and pro-IL-18 in the bowel specimens from patients with HSCR and controls.
methodsPulled-through colonic specimens were collected from HSCR patients (n = 6) and healthy controls from the proximal colostomy of children with anorectal malformations (n = 6). The gene expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1β and pro-IL-18 was assessed using qPCR. The protein distribution was assessed using immunofluorescence and confocal microscopy. MAIN
resultsqRT-PCR analysis revealed that NLRP3, NLRP12, NLRC4, ASC and pro-IL-1β gene expressions was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls. Confocal microscopy revealed a markedly decreased expression of NLRP3, NLRP12, NLRC4 and ASC protein in the colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls.
conclusionsTo our knowledge, this is the first study analyzing NLRP3, NLRP12, NLRC4, ASC and pro-IL-1β gene expressions in patients with HSCR. Decreased expression of NLRP3, NLRP12, NLRC4, ASC and pro-IL-1β in the aganglionic and ganglionic bowel may increase susceptibility of HSCR patients to develop HAEC.
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