title: High ACSL5 transcript levels associate with systemic lupus erythematosus and apoptosis in Jurkat T lymphocytes and peripheral blood cells.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which increased apoptosis and decreased apoptotic cells removal has been described as most relevant in the pathogenesis. Long-chain acyl-coenzyme A synthetases (ACSLs) have been involved in the immunological dysfunction of mouse models of lupus-like autoimmunity and apoptosis in different in vitro cell systems. The aim of this work was to assess among the ACSL isoforms the involvement of ACSL2, ACSL4 and ACSL5 in SLE pathogenesis.
  
  
  RESULTS
  With this end, we determined the ACSL2, ACSL4 and ACSL5 transcript levels in peripheral blood mononuclear cells (PBMCs) of 45 SLE patients and 49 healthy controls by quantitative real time-PCR (q-PCR). We found that patients with SLE had higher ACSL5 transcript levels than healthy controls [median (range), healthy controls = 16.5 (12.3-18.0) vs. SLE = 26.5 (17.8-41.7), P = 3.9×10 E-5] but no differences were found for ACSL2 and ACSL4. In in vitro experiments, ACSL5 mRNA expression was greatly increased when inducing apoptosis in Jurkat T cells and PBMCs by Phorbol-Myristate-Acetate plus Ionomycin (PMA+Io). On the other hand, short interference RNA (siRNA)-mediated silencing of ACSL5 decreased induced apoptosis in Jurkat T cells up to the control levels as well as decreased mRNA expression of FAS, FASLG and TNF.
  
  
  CONCLUSIONS
  These findings indicate that ACSL5 may play a role in the apoptosis that takes place in SLE. Our results point to ACSL5 as a potential novel functional marker of pathogenesis and a possible therapeutic target in SLE.
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra-Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Catalá-Rabasa
authors.forename: Dorothy
authors.initials: D
authors.lastname: Ndagire
authors.forename: Jose Mario
authors.initials: JM
authors.lastname: Sabio
authors.forename: Maria
authors.initials: M
authors.lastname: Fedetz
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
mesh_terms: D000328:Adult; D017209:Apoptosis; D019540:Area Under Curve; D001327:Autoimmune Diseases / Q000235:genetics; D003066:Coenzyme A Ligases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012044:Regression Analysis
chemical_list: D005819:Genetic Markers; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D003066:Coenzyme A Ligases; C485465:ACSL5 protein, human