Regulation of B cell activating factor (BAFF) receptor expression by NF-kappaB signaling in rheumatoid arthritis B cells.
10.3858/emm.2011.43.6.038
- Author:
Yun Ju WOO
1
;
Bo Young YOON
;
Joo Yeon JHUN
;
Hye Jwa OH
;
Sewon MIN
;
Mi La CHO
;
Sung Hwan PARK
;
Ho Youn KIM
;
Jun Ki MIN
Author Information
1. The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea. iammila@catholic.ac.kr, rmin6403@hanmail.net
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
B-cell activation factor receptor;
B-cell activating factor;
B-lymphocytes;
NF-kappaB;
rheumatoid arthritis
- MeSH:
Arthritis, Rheumatoid/genetics/*metabolism/pathology/physiopathology;
B-Cell Activating Factor/genetics/metabolism;
B-Cell Activation Factor Receptor/genetics/*metabolism;
B-Lymphocytes/*drug effects/immunology/metabolism/pathology;
Cell Separation;
Cells, Cultured;
Disease Progression;
Enzyme Inhibitors/pharmacology;
Flow Cytometry;
Gene Expression Regulation/immunology;
Humans;
Immunohistochemistry;
NF-kappa B/*metabolism;
Signal Transduction/immunology;
Synovial Membrane/*pathology;
T-Lymphocytes/drug effects/immunology/metabolism/pathology;
Transcriptional Activation/drug effects
- From:Experimental & Molecular Medicine
2011;43(6):350-357
- CountryRepublic of Korea
- Language:English
-
Abstract:
B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-kappaB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-kappaB inhibitors. NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-kappaB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-kappaB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-kappaB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.
