Affiliation:
1. Laboratory of Virology, Institute of Pathology B23, University of Liège, B-4000 Liège, Belgium
2. Laboratory of Molecular and Cellular Genetics, URA CNRS 1135, Université Pierre et Marie Curie, F-75230 Paris Cedex 05, France
Abstract
Reactive oxygen species (ROS) such as hydrogen peroxide serve as second messengers in the induction of the transcription factor NF-κB, and hence in the activation and replication of human immunodeficiency virus type 1 (HIV-1) in human cells. During inflammatory reactions, many oxidative species are produced, one of which is hypochlorous acid (HOCl), which is responsible for the microbicidal effects of activated human polymorphonuclear leukocytes. Treatment of a T-lymphocytic cell line with micromolar concentrations of HOCl promoted the appearance of transcription factor NF-κB (the heterodimer p50/p65) in the nucleus of the cells, even in the absence of de novo protein synthesis. Western blot analysis of the NF-κB inhibitory subunits (IκB) demonstrated that both IκB-α proteolysis and p105 processing were induced by the treatment. NF-κB activation was very effective when cells were subjected to hyperthermia before being treated with HOCl. Various antioxidants, such as pyrrolidine dithiocarbamate, p-bromophenacyl-bromide and nordihydroguaiaretic acid could strongly reduce NF-κB translocation, demonstrating the importance of oxidative species in the transduction mechanism. Moreover, ACH-2 cells treated with HOCl or H2O2 released tumour necrosis factor-α (TNF-α) in the supernatants. The importance of TNF-α release in NF-κB induction by HOCl or H2O2 was demonstrated by the fact that: (1) the nuclear appearance of NF-κB was promoted in untreated cells; and (2) synergism between TNF-α and HOCl was detected. Collectively, these results suggest that HOCl should be considered as an oxidative species capable of inducing NF-κB in a T-lymphocytic cell line through a transduction mechanism involving ROS, and having a long-distance effect through subsequent TNF-α release.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
135 articles.
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