Ligation of CD40 receptor in human B lymphocytes triggers the 5-lipoxygenase pathway to produce reactive oxygen species and activate p38 MAPK.
10.3858/emm.2011.43.2.012
- Author:
Yun Jung HA
1
;
Hee Jung SEUL
;
Jong Ran LEE
Author Information
1. Division of Life and Pharmaceutical Sciences, College of Natural Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea. jrlee@ewha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antigens, CD40;
arachidonate 5-lipoxygenase;
B-lymphocytes;
p38 mitogen-activated protein kinases;
phosphatidylinositol 3-kinase;
reactive oxygen species
- MeSH:
Antigens, CD40/*metabolism;
Arachidonate 5-Lipoxygenase/*metabolism;
B-Lymphocytes/*enzymology/immunology;
CD40 Ligand/metabolism;
Cell Line, Tumor;
*Enzyme Activation;
HEK293 Cells;
Humans;
Phosphatidylinositol 3-Kinases/metabolism;
Protein Binding;
*Reactive Oxygen Species/metabolism;
Signal Transduction;
p38 Mitogen-Activated Protein Kinases/*metabolism;
rac GTP-Binding Proteins/metabolism
- From:Experimental & Molecular Medicine
2011;43(2):101-110
- CountryRepublic of Korea
- Language:English
-
Abstract:
Previously, we reported that CD40-induced production of reactive oxygen species (ROS) by NADPH oxidase requires the TNF receptor-associated factor (TRAF) 3, as well as the activities of phosphatidylinositol 3-kinase (PI3K) and Rac1. Here we investigated the possible mechanisms of the production of ROS after CD40 ligation in B cells. We describe an alternative ROS production pathway that is triggered by CD40 ligation, involves 5-lipoxygenase (5-LO), and results in activation of p38 MAPK. Our studies in Raji human B lymphomas revealed that CD40-induced ROS production by 5-LO also requires the activities of PI3K and Rac1. In contrast to the NADPH oxidase pathway, however, TRAF molecules are not required for the CD40-induced ROS production by 5-LO. The association of CD40 with 5-LO is dependent on CD40 ligation in Raji B cells, and co-immunoprecipitation experiments using epitope-tagged proteins transiently expressed in human embryonic kidney 293T cells revealed the role of the regulatory subunit of PI3K, p85, in this association. Collectively, these data suggest a separate pathway for the CD40-induced ROS production in B cells and demonstrate that this pathway requires 5-LO via direct association of p85 with both CD40 and 5-LO.
