title: Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.
abstract: Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Chung-Che
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Kuo
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Hong
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Yeh
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Kuo-Shun
authors.initials: KS
authors.lastname: Shih
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Du
authors.affiliation: a Institute of Molecular and Cellular Biology, National Tsing Hua University ; Hsinchu , Taiwan.|b Department of Life Science ; National Tsing Hua University ; Hsinchu , Taiwan.
authors.forename: Hua-Wen
authors.initials: HW
authors.lastname: Fu
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D016480:Helicobacter pylori / Q000276:immunology* / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D037342:Pertussis Toxin / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D019204:GTP-Binding Proteins; D015850:Interleukin-6; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases; C508600:IL6 protein, human; C092412:neutrophil-activating protein A, Helicobacter pylori
keywords: HP-NAP; Helicobacter pylori neutrophil-activating protein; PTX; TLR2; mast cells