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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzymeAoxidase 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-1α and IL-1β 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 (US)
Pages (from-to)2568-2575
Number of pages8
JournalEndocrinology
Volume153
Issue number6
DOIs
StatePublished - Jun 2012

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'The inflammatory response in Acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy)'. Together they form a unique fingerprint.

Cite this