title: Vibrio vulnificus IlpA induces MAPK-mediated cytokine production via TLR1/2 activation in THP-1 cells, a human monocytic cell line.
abstract: Vibrio vulnificus is a pathogenic bacterium causing primary septicemia, which is followed by 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 with TLR6. MyD88 was necessary for IlpA-induced cytokine expression through TLR1/TLR2. Three mitogen activated protein kinases (MAPK), 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-κB) 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-κB/AP-1 comprises the signaling pathway responsible for proinflammatory cytokine production by V. vulnificus IlpA.
authors: Department of Environmental Medical Biology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors: Na Yeon
authors: NY
authors: Lee
authors: Hye-Yeon
authors: HY
authors: Lee
authors: Kyu-Ho
authors: KH
authors: Lee
authors: Seung Hyun
authors: SH
authors: Han
authors: Soon-Jung
authors: SJ
authors: Park
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008074:Lipoproteins / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051194:Toll-Like Receptor 1 / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D041261:Vibrio vulnificus / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008074:Lipoproteins; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D020928:Mitogen-Activated Protein Kinases