The inflammatory response in Acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy)

H.I. El Hajj, A. Vluggens, P. Andreoletti, K. Ragot, S.J. Mandard, A.H. Kersten, H.R. Waterham, G. Lizard, R.J.A. Wanders, J.K. Reddy, M. Cherkaoui-Malki

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)


Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzyme A oxidase 1 (ACOX1) deficiency, which leads to the accumulation of very-long-chain fatty acids (VLCFA) and inflammatory demyelination. However, the components of this inflammatory process in P-NALD remain elusive. In this study, we used transcriptomic profiling and PCR array analyses to explore inflammatory gene expression in patient fibroblasts. Our results show the activation of IL-1 inflammatory pathway accompanied by the increased secretion of two IL-1 target genes, IL-6 and IL-8 cytokines. Human fibroblasts exposed to very-long-chain fatty acids exhibited increased mRNA expression of IL-1a and IL-1ß cytokines. Furthermore, expression of IL-6 and IL-8 cytokines in patient fibroblasts was down-regulated by MAPK, p38MAPK, and Jun N-terminal kinase inhibitors. Thus, the absence of acyl-coenzyme A oxidase 1 activity in P-NALD fibroblasts triggers an inflammatory process, in which the IL-1 pathway seems to be central. The use of specific kinase inhibitors may permit the modulation of the enhanced inflammatory status.
Original languageEnglish
Pages (from-to)2568-2575
Issue number6
Publication statusPublished - 2012


  • x-linked adrenoleukodystrophy
  • multiple-sclerosis lesions
  • nf-kappa-b
  • peroxisomal disorders
  • chemokine receptors
  • microarray analysis
  • in-vitro
  • interleukin-1
  • cells
  • gene

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