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.
Jeon
Sung-Tak
ST
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
Kim
Won-Jung
WJ
Lee
Sang-Min
SM
Lee
Min-Young
MY
Park
Seung-Beom
SB
Lee
Seung-Hee
SH
Kim
In-San
IS
Suk
Kyoungho
K
Choi
Beom Kyu
BK
Choi
Eun M
EM
Kwon
Byoung S
BS
Lee
Won-Ha
WH
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