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Characterization of signaling pathways for immune response induced by a recombinant lipoprotein, IlpA of Vibrio vulnificus

Issue Date
2011
Description
Dept. of Medical Science/박사
Abstract
Vibrio vulnificus is a pathogenic bacterium that causes primary septicemia, which follows a classical septic shock pathway including an overwhelming inflammatory cytokine response. V. vulnificus IlpA is a potent immunogenic lipoprotein that triggers cytokine production in human monocytes by activating the toll-like receptor 2 (TLR2). In this study, we further defined the IlpA signaling pathways involved in cytokine production in the human monocytic cell line, THP-1. TLR2 was involved in cytokine production by complexing with TLR1, but not TLR6. MyD88 was necessary for IlpA-induced cytokine expression through TLR1/2. Three mitogen activated protein kinases (MAPKs), p38, ERK1/2, and JNK, were activated in THP-1 cells stimulated with recombinant IlpA (rIlpA). Selective inhibition of each MAPK resulted in significant decrease of rIlpA-induced cytokine production. Especially, functional TLR2 was necessary for IlpA-induced activation of p38 and JNK. IlpA augmented the DNA-binding activity of nuclear factor-kappaB (NF-B) and activator protein-1 (AP-1) transcriptional factors to their recognition sites in THP-1 cells. These results suggest that serial activation of TLR1/TLR2, MyD88, the three MAPKs, and NF-B/AP-1 comprises the signaling pathways responsible for proinflammatory cytokine production by V. vulnificus IlpA.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/134048
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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