TY - JOUR
T1 - Mechanisms of human lymphotoxin beta receptor activation on upregulation of CCL5/RANTES production
AU - Yeh, Diana Yu Wung
AU - Wu, Chia Chang
AU - Chin, Yi Ping
AU - Lu, Chia Jung
AU - Wang, Yuan Hung
AU - Chen, Mei Chieh
N1 - Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - Human lymphotoxin-β receptor (LTβR), a member of the tumor necrosis factor receptor superfamily, plays an essential role in secondary lymphoid organ development, host defense, chemokine secretion, and apoptosis. In our study, LTβR activations by different stimulations were all found to induce RANTES secretion. Overexpression of LTβR or stimulation LTβR by ligands or agonistic antibody in human lung epithelial cells induced RANTES secretion However, the regulatory mechanism and the signaling cascade have not been fully elucidated. Therefore, the aim of this study was to elucidate the mechanism underlying LTβR-mediated RANTES production. Our study indicated that activation of JNK and ERK was important for the regulation of RANTES secretion. In addition, dominant negative mutants of ASK1, TAK1, and MEKK1 inhibited LTβR-induced RANTES expression. The dominant negative mutants of TRAF2, 3, and 5 also inhibited LTβR-mediated RANTES secretion. Chromatin immunoprecipitation analysis showed that LTβR activation induced the binding of c-Jun and NF-κB to the RANTES promoter. The results of this study show that LTβR activates ASK1, TAK1, and MEKK1 cascades via TRAF2, 3, and 5, resulting in the activation of JNK and ERK, which promotes the binding of c-Jun and NF-κB to the RANTES promoter, thereby increasing RANTES expression and secretion.
AB - Human lymphotoxin-β receptor (LTβR), a member of the tumor necrosis factor receptor superfamily, plays an essential role in secondary lymphoid organ development, host defense, chemokine secretion, and apoptosis. In our study, LTβR activations by different stimulations were all found to induce RANTES secretion. Overexpression of LTβR or stimulation LTβR by ligands or agonistic antibody in human lung epithelial cells induced RANTES secretion However, the regulatory mechanism and the signaling cascade have not been fully elucidated. Therefore, the aim of this study was to elucidate the mechanism underlying LTβR-mediated RANTES production. Our study indicated that activation of JNK and ERK was important for the regulation of RANTES secretion. In addition, dominant negative mutants of ASK1, TAK1, and MEKK1 inhibited LTβR-induced RANTES expression. The dominant negative mutants of TRAF2, 3, and 5 also inhibited LTβR-mediated RANTES secretion. Chromatin immunoprecipitation analysis showed that LTβR activation induced the binding of c-Jun and NF-κB to the RANTES promoter. The results of this study show that LTβR activates ASK1, TAK1, and MEKK1 cascades via TRAF2, 3, and 5, resulting in the activation of JNK and ERK, which promotes the binding of c-Jun and NF-κB to the RANTES promoter, thereby increasing RANTES expression and secretion.
KW - LTβR
KW - MAPK
KW - NF-κB
KW - RANTES
KW - TRAF
KW - c-Jun
UR - http://www.scopus.com/inward/record.url?scp=84934888246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84934888246&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2015.06.010
DO - 10.1016/j.intimp.2015.06.010
M3 - Article
C2 - 26096887
AN - SCOPUS:84934888246
SN - 1567-5769
VL - 28
SP - 220
EP - 229
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 1
ER -