Dissemin is shutting down on January 1st, 2025

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Oxford University Press, Endocrinology, 6(153), p. 2568-2575, 2012

DOI: 10.1210/en.2012-1137

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The Inflammatory Response in Acyl-CoA Oxidase 1 Deficiency (Pseudoneonatal Adrenoleukodystrophy)

Journal article published in 2012 by Hammam I. El Hajj, Aurore Vluggens, Pierre Andreoletti ORCID, Kevin Ragot, Stéphane Mandard ORCID, Sander Kersten, Hans R. Waterham, Gérard Lizard, Ronald J. A. Wanders, Janardan K. Reddy, Mustapha Cherkaoui-Malki
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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-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.