Reverse signaling through BAFF differentially regulates the expression of inflammatory mediators and cytoskeletal movements in THP-1 cells.
Most members of the tumor-necrosis factor superfamily have been reported to mediate reverse signaling in T cells, macrophages, and/or dendritic cells. BAFF has been reported to have important functions in B-cell survival through forward signaling, but the presence of reverse signaling has not been explored. To investigate the possibility of BAFF-mediated reverse signaling, the expression patterns and functions of BAFF were analyzed in monocytic cell lines including the human macrophage-like cell line, THP-1. The expression of BAFF and its receptors was detected in monocytic cell lines, either before or after activation. The stimulation of BAFF induced the expression of matrix metalloproteinase (MMP)-9, interleukin -8, and transforming growth factor-beta-induced gene product (beta ig-h3) and the upregulation of intercellular adhesion molecule-1 in THP-1 cells. The activation of mitogen-activated protein kinase extracellular signal-regulated kinase1/2 and nuclear factor-kappaB was required for these responses. In addition to these stimulatory effects, BAFF-mediated signaling inhibited processes involving cytoskeletal movement such as phagocytosis and transmigration through blocking the activation of phosphatidylinositol 3-kinase/AKT and Rac-1. Furthermore, murine primary macrophage culture such as peritoneal macrophages expressed BAFF and stimulation of it induced the expression of MMP-9. These observations show that the reverse signaling initiated from BAFF induces the expression of inflammatory mediators while suppressing the cytoskeletal movements associated with phagocytosis and transmigration.
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
Sung-Tak
ST
Jeon
Won-Jung
WJ
Kim
Sang-Min
SM
Lee
Min-Young
MY
Lee
Seung-Beom
SB
Park
Seung-Hee
SH
Lee
In-San
IS
Kim
Kyoungho
K
Suk
Beom Kyu
BK
Choi
Eun M
EM
Choi
Byoung S
BS
Kwon
Won-Ha
WH
Lee
D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099222:betaIG-H3 Protein
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D020780:Matrix Metalloproteinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016212:Transforming Growth Factor beta; D015054:Zymosan; D020830:rac1 GTP-Binding Protein; D000099222:betaIG-H3 Protein; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human