Involvement of JNK and NF-κB pathways in lipopolysaccharide (LPS)-induced BAG3 expression in human monocytic cells.
Lipopolysaccharide (LPS) is an outer-membrane glycolipid component of Gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. Bcl-2-associated athanogene 3 (BAG3) is a survival protein that has been shown to be stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, proteasome inhibition, and human immunodeficiency virus 1 (HIV-1) infection. In addition, BAG3 regulates replication of Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) replication, suggesting that BAG3 could participate in the host response to infection. In the current study, we found that LPS increased the expression of BAG3 in a dose- and time-dependent manner. Actinomycin D completely blocked the LPS-induced BAG3 accumulation, as well as LPS activated the proximal promoter of BAG3 gene, supported that the induction by LPS occurred at the level of gene transcription. LPS-induced BAG3 expression was blocked by JNK or NF-κB inhibition, suggesting that JNK and NF-κB pathways participated in BAG3 induction by LPS. In addition, we also found that induction of BAG3 was implicated in monocytic cell adhesion to extracellular matrix induced by LPS. Overall, the data support that BAG3 is induced by LPS via JNK and NF-κB-dependent signals, and involved in monocytic cell-extracellular matrix interaction, suggesting that BAG3 may have a role in the host response to LPS stimulation.
Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China. wanghq_doctor@hotmail.com
Hua-Qin
HQ
Wang
Xin
X
Meng
Bao-Qin
BQ
Liu
Chao
C
Li
Yan-Yan
YY
Gao
Xiao-Fang
XF
Niu
Ning
N
Li
Yifu
Y
Guan
Zhen-Xian
ZX
Du
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D005353:Fibronectins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048031:JNK Mitogen-Activated Protein Kinases