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

Virulence. 2015;6(8):755-65. doi: 10.1080/21505594.2015.1043505. Epub 2015 Sep 16.


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.

Keywords: HP-NAP; Helicobacter pylori neutrophil-activating protein; PTX; TLR2; mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / immunology*
  • Bacterial Proteins / pharmacology
  • Cell Line
  • GTP-Binding Proteins / immunology*
  • GTP-Binding Proteins / metabolism
  • HEK293 Cells
  • Helicobacter pylori / immunology*
  • Helicobacter pylori / metabolism
  • Histamine Release / drug effects
  • Histamine Release / immunology*
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • MAP Kinase Signaling System
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mast Cells / microbiology*
  • Neutrophils / immunology
  • Neutrophils / microbiology
  • Pertussis Toxin / metabolism
  • Pertussis Toxin / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / immunology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Toll-Like Receptor 2
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Bacterial Proteins
  • IL6 protein, human
  • Interleukin-6
  • Toll-Like Receptor 2
  • neutrophil-activating protein A, Helicobacter pylori
  • Pertussis Toxin
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • GTP-Binding Proteins