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Correlation between NF-κB signal pathway-mediated caspase-4 activation and Kawasaki disease

Jing Tian1, Xinjiang An1, Ling Niu1

  • 1Department of Cardiology, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221002, P.R. China.

Experimental and Therapeutic Medicine
|June 8, 2017
PubMed

Insights

Nuclear factor-kappa B (NF-κB) activation drives caspase-4 expression, leading to inflammatory cytokine release and endothelial cell injury in Kawasaki disease (KD). Inhibiting NF-κB reduces these effects, highlighting its critical role in KD pathogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Kawasaki disease (KD) is an acute febrile vasculitis affecting young children, characterized by inflammation of medium-sized arteries, particularly coronary arteries.
  • The precise molecular mechanisms underlying KD-induced endothelial cell injury and inflammation remain incompletely understood.
  • Nuclear factor-kappa B (NF-κB) signaling is implicated in inflammatory processes, but its specific role in KD pathogenesis, particularly concerning caspase-4 activation, requires elucidation.

Purpose of the Study:

  • To investigate the role and mechanisms of NF-κB-mediated caspase-4 activation in inducing inflammatory cytokines during Kawasaki disease (KD).
  • To examine the impact of NF-κB and caspase-4 on coronary artery endothelial cell (HCAEC) injury and apoptosis in KD.
  • To determine the therapeutic potential of inhibiting NF-κB in mitigating KD-related cellular damage.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from KD patients and healthy controls were cultured and stimulated.
  • Tumor necrosis factor-alpha (TNF-α) levels were measured using ELISA.
  • Human coronary artery endothelial cells (HCAECs) were treated with KD patient-derived PBMC supernatant to assess NF-κB p65 activation, caspase-4 expression, cytokine secretion (IL-6, IL-1β), and apoptosis via Western blot, immunofluorescence, ELISA, and Annexin V/PI staining.
  • NF-κB inhibition was achieved using SN50.

Main Results:

  • Stimulated PBMCs from KD patients exhibited significantly higher TNF-α secretion compared to controls.
  • HCAECs treated with KD patient PBMC supernatant showed significantly elevated NF-κB p65 and caspase-4 expression, along with increased IL-6, IL-1β secretion, and apoptosis.
  • NF-κB inhibition with SN50 significantly attenuated caspase-4 expression, inflammatory cytokine secretion, and HCAEC apoptosis.

Conclusions:

  • NF-κB signaling pathway activation is crucial in Kawasaki disease.
  • NF-κB induces inflammatory factors (IL-6, IL-1β) and mediates caspase-4 expression in HCAECs, contributing to endothelial cell apoptosis and injury.
  • NF-κB-mediated caspase-4 expression plays a critical role in the pathogenesis of Kawasaki disease, representing a potential therapeutic target.

Keywords:
Kawasaki diseasecaspase-4human coronary artery endothelial cellsnuclear factor-κB

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