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The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset

  • Kartiga Natarajan , Gokila Devi Mathialagan , Somasundaram Raghavan and Narkunaraja Shanmugam EMAIL logo
Published/Copyright: October 15, 2015
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Cellular and Molecular Biology Letters
From the journal Cellular and Molecular Biology Letters Volume 20 Issue 4

Abstract

Malondialdehyde (MDA) is a highly reactive endogenous product of thromboxane synthesis in the prostagland and lipid peroxidation by reactive oxygen species. Elevated MDA levels occur in diabetes and atherosclerotic plaques. The aim of this study was to examine the molecular mechanisms of MDA-induced IL-17E cytokine expression and its effect on T-cell differentiation. Real-time PCR, RT-PCR and ELISA were used to assess the expression of IL-17 family cytokines in Jurkat T-cells and human peripheral blood lymphocytes (PBLCs) from diabetic subjects. Luciferase reporter assays were used for the promoter activation study. Pharmacological inhibitors were used for signaling pathway experiments. FACS analyses were used to measure the Th1, Th2 and Th17 subset levels. MDA induced significant (2- to 3-fold; p < 0.01) generation of IL-17E mRNA in a dose- and time-dependent manner in Jurkat T-cells and PBLCs. Elevated IL-17E mRNA levels were found in the lymphocytes from diabetic subjects. The increased IL-17E protein and mRNA levels correlate well with serum MDA levels from diabetic patients. Transient transfection of plasmid containing the minimum IL-17E promoter region (pIL-17E-Luc) showed a significant (2-fold; p < 0.01) increase in luciferase activity. Pretreatment of lymphocytes with pharmacological inhibitors showed the involvement of antioxidant, NF-ƙB, p38MAPK, PKC and ERK signaling pathways. Quantification of the Th1, Th2 and Th17 cell population in PBLCs via FACS analyses revealed an increase in the Th17 subset. These results show that MDA transcriptionally upregulates the expression of IL-17E in lymphocytes and alters lymphocyte differentiation towards the pathogenic Th17 subset.

Keywords : Malondialdehyde; IL-17E; Lymphocyte; Th cells; Skewing; mRNA expression; Promoter activation; Diabetes; Inflammation; Advanced glycation/lipoxidation

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Received: 2015-3-2
Accepted: 2015-8-6
Published Online: 2015-10-15
Published in Print: 2015-12-1

© 2015

Articles in the same Issue

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  2. HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
  3. Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?
  4. The transition of the 37-kDa laminin receptor (RPSA) to higher molecular weight species: SUMOylation or artifact?
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  6. Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β
  7. Bioinformatics-based molecular classification of Arthrobacter plasmids
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  9. The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset
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https://doi.org/10.1515/cmble-2015-0038
Keywords for this article
Malondialdehyde; IL-17E; Lymphocyte; Th cells; Skewing; mRNA expression; Promoter activation; Diabetes; Inflammation; Advanced glycation/lipoxidation

Articles in the same Issue

  1. Elevated pressure enhanced TRAIL-induced apoptosis in hepatocellular carcinoma cells via ERK1/2-inactivation
  2. HsOrc4-dependent DNA remodeling of the ori-β DHFR replicator
  3. Is Iron Chelation Important in Preventing Glycation of Bovine Serum Albumin in Vitro?
  4. The transition of the 37-kDa laminin receptor (RPSA) to higher molecular weight species: SUMOylation or artifact?
  5. Mechanical strain affects some microRNA profiles in pre-oeteoblasts.
  6. Sphingosine-1-phosphate induces the migration and angiogenesis of EPCs through the Akt signaling pathway via sphingosine-1-phosphate receptor 3/platelet-derived growth factor receptor-β
  7. Bioinformatics-based molecular classification of Arthrobacter plasmids
  8. Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout
  9. The advanced lipoxidation end product precursor malondialdehyde induces IL-17E expression and skews lymphocytes to the Th17 subset
  10. On Application of Langevin Dynamics in Logarithmic Potential to Model Ion Channel Gate Activity
  11. Superoxide Dismutase 2 Polymorphisms and Osteoporosis in Asian Indians: A Genetic Association Analysis
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