Journal of Southern Medical University ›› 2005, Vol. 25 ›› Issue (05): 493-497.

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Advanced oxidation protein products-induced tumor necrosis factor α secretion in monocytes via reactive oxygen species generation

ZHANG Zhi-hui, LIU Shang-xi, HOU Fan-fan, TIAN Jian-wei, WANG Li, LIU Zhi-qiang, CHEN Yuan   

  1. 南方医科大学南方医院肾内科, 广东, 广州, 510515
  • Online:2005-05-20 Published:2005-05-20

Abstract: Objective To investigate the effect of advanced oxidation protein products (AOPP) on the secretion of tumor necrosis factor α (TNFα) in monocytes and its possible mechanism.Method Human monocyte cell line THP-1 and peripheral blood monocytes were incubated with AOPP-bovine serum albumin(BSA) prepared by incubation of BSA with hypochlorous acid. TNFα in the supernatant of the culture medium of THP-1 cells was measured by enzyme-linked immunosorbent assay and the production of reactive oxygen species (ROS) evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescin using Wallac 1420 multilabel counter. The intracellular signal was observed by pre-treatment of the cells with antioxidant pyrrolidine dithiocarbamate, NADPH oxidase inhibitor apocynin or p38 phosphorylation inhibitor SB203580.Results AOPP-BSA induced TNF-α secretion and ROS production in monocytes. Pretreatment of the cells with pyrrolidine dithiocarbamate scavenged most of ROS and almost completely blocked TNF-α secretion induced by AOPP-BSA. Inhibition of NADPH oxidase by apocynin and p38 phosphorylation by SB203580 could both effectively block AOPP-BSA-induced TNF-α secretion.Conclusion AOPP-BSA induced TNF-α secretion in monocytes, and the intracellular signaling involves ROS produced by activated NADPH oxidase and subsequent p38 phosphorylation.

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