Alpha-lipoic acid inhibits TNF-alpha induced NF-kappa B activation through blocking of MEKK1-MKK4-IKK signaling cascades

International Immunopharmacology
Chang-Keun LeeBin Yoo

Abstract

The therapeutic effects of alpha-lipoic acid (alpha-LA) via NF-kappa B down regulation were demonstrated on joint inflammation and erosion in an animal model. In this study, we investigated how alpha-LA inhibits the pathway of NF-kappa B activation by TNF-alpha via the mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis (RA) fibroblast-like synovial cells (FLS). FLS were stimulated with TNF-alpha following pre-treatment with or without alpha-LA. Electrophoretic mobility shift assays (EMSA) revealed that TNF-alpha activates NF-kappa B in FLS. This was inhibited by alpha-LA at concentrations of 1 mM. TNF-alpha induced IKK mediated phosphorylation of GST-I kappa B and pre-treatment with alpha-LA inhibited this pathway. FLS constitutively express MEKK1, MEKK2, MEKK3, and TAK1 and that their levels are unaffected by TNF-alpha or alpha-LA. Immunoprecipitation using anti-MEKK1 antibody phosphorylated GST-I kappa B and pre-treating the cells with alpha-LA could abolish the reaction. FLS were immunoprecipitated using an antibody to MEKK1, and MKK4 was coprecipitated with MEKK1. In addition, immune complexes precipitated with anti-MKK4 antibody phosphorylated GST-I kappa B, and pre-treatment with alpha-LA inhibited th...Continue Reading

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Citations

Jun 29, 2010·Archives of Animal Nutrition·Pengfei HanJingdong Yin
May 29, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kyung Pyo KangWon Kim
Mar 10, 2015·Journal of the American College of Nutrition·Elham MirtaheriMehran Mesgari Abbasi
Jun 14, 2016·Expert Opinion on Drug Delivery·Giovanni MonastraVittorio Unfer
Apr 25, 2019·BioMed Research International·Wei LiuSheng-Guang Li
Jun 9, 2020·Oxidative Medicine and Cellular Longevity·Abdullah F AlAsmariAli A Alshamrani
Nov 10, 2020·Environmental Science and Pollution Research International·Khalid Shaaban HashemMohamed M Abdel-Daim
Sep 13, 2011·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Tannaz KhabbaziParvin Pour-Abdollahi
Aug 5, 2010·Journal of Agricultural and Food Chemistry·Yuan-Shu LaiTz-Chong Chou

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