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Role of TNF Receptor-Associated Factor 3 in the CD40 Signaling by Production of Reactive Oxygen Species through Association with p40 phox, a Cytosolic Subunit of Nicotinamide Adenine Dinucleotide Phosphate Oxidase
- Role of TNF Receptor-Associated Factor 3 in the CD40 Signaling by Production of Reactive Oxygen Species through Association with p40 phox, a Cytosolic Subunit of Nicotinamide Adenine Dinucleotide Phosphate Oxidase
- Ha Y.J.; Lee J.R.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Immunology
- vol. 172, no. 1, pp. 231 - 239
- SCI; SCIE; SCOPUS
- To extend our previous report, which showed the production of the reactive oxygen species (ROS) after the CD40 ligation in the B cells, we further examined the possible mechanisms for ROS production and the involvement of CD40-induced ROS in p38 activation. Our research shows that the stimulation of WEHI 231 B lymphomas with anti-CD40 induced ROS production and p38 activation. An antioxidant N-acetyl-L-cysteine or an inhibitor for NADPH oxidase blocked both of these, but the inhibitors for 5-lipoxygenase did not. We also show that the treatment of cells with inhibitors for the phosphatidylinositol 3-kinase (PI3-K) interfered with the CD40-induced ROS production and p38 activation. In addition, when overexpressed with a dominant negative form of either Rac1 (N17Rac1) or the TNFR-associated factor (TRAF) 3, the WEHI 231 B cells did not show a full response to the CD40 stimulation to produce ROS. Molecular association studies further revealed that the TRAF3 association with p40 phox, a cytosolic subunit of NADPH oxidase and p85 (a subunit of PI3-K), may possibly be responsible for the production of ROS by CD40 stimulation in WEHI 231 B cells. Collectively, these data suggest that the CD40-induced ROS production by NADPH oxidase in WEHI 231 requires the role of TRAF3, as well as activities of PI3-K and Rac1.
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