Pediatric Surgery International

, Volume 35, Issue 1, pp 15–20 | Cite as

Altered expression of inflammasomes in Hirschsprung’s disease

  • Hiroki Nakamura
  • Anne Marie O’Donnell
  • Naoum Fares Marayati
  • Christian Tomuschat
  • David Coyle
  • Prem PuriEmail author
Original Article


Aim of the study

The 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.


Pulled-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 results

qRT-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.


To 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.


Inflammasome Enterocolitis Hirschsprung's disease 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hiroki Nakamura
    • 1
  • Anne Marie O’Donnell
    • 1
  • Naoum Fares Marayati
    • 2
  • Christian Tomuschat
    • 1
    • 3
  • David Coyle
    • 1
  • Prem Puri
    • 1
    • 4
    Email author
  1. 1.National Children’s Research CentreOur Lady’s Children’s HospitalDublinIreland
  2. 2.Department of PsycologyPrinceton UniversityPrincetonUSA
  3. 3.Department of Pediatric SurgeryChildren’s Hospital at WestmeadNew South WalesAustralia
  4. 4.School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research University College DublinDublinIreland

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