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

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.

• Authors: 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
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 6 Pg. 2568-75 (Jun 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22508517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids
• Inflammation Mediators
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Osteopontin
• hexacosanoic acid
• Acyl-CoA Oxidase

Topics

• Acyl-CoA Oxidase (deficiency, genetics, metabolism)
• Cells, Cultured
• Fatty Acids (pharmacology)
• Fibroblasts (drug effects, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Humans
• Immunohistochemistry
• Inflammation (genetics, metabolism)
• Inflammation Mediators (metabolism)
• Interleukin-1 (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Interleukin-8 (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Osteopontin (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcriptome