期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms222111560
关键词
Helicobacter pylori neutrophil-activating protein; HP-NAP; TLR2; HL-60 cells; neutrophils; IL-8; PTX; ROS
资金
- Ministry of Science and Technology of Taiwan [MOST110-2311-B-007-002, MOST108-2311-B-007-004, MOST107-2311-B-007-004, MOST104-2311-B-007-003]
- Mackay Memorial Hospital, Taiwan [MMH-TH-11007, MMH-TH-10906, MMH-TH-10808]
- National Tsing Hua University, Taiwan [110Q2522E1, 109Q2521E1, 108Q2522E1, 106N528CE1, 105N528CE1, 104N2052E1]
TLR2 is involved in HP-NAP-induced IL-8 secretion in neutrophils and ATRA-induced differentiated HL-60 cells, while not involved in ROS production. Additionally, PTX-sensitive G proteins contribute to HP-NAP-induced IL-8 secretion in both types of cells.
Helicobacter pylori neutrophil-activating protein (HP-NAP)-induced production of reactive oxygen species (ROS) by neutrophils and monocytes is regulated by pertussis toxin (PTX)-sensitive G proteins, whereas HP-NAP-induced cytokine secretion by monocytes is mediated by Toll-like receptor 2 (TLR2). However, it is unclear whether TLR2 participates in HP-NAP-induced cytokine secretion by neutrophils. Here, all-trans retinoic acid (ATRA)-induced differentiated HL-60 cells were first employed as a neutrophil model to investigate the molecular mechanisms underlying neutrophil responses to HP-NAP. HP-NAP-induced ROS production in ATRA-induced differentiated HL-60 cells is mediated by the PTX-sensitive heterotrimeric G protein-dependent activation of extracellular signal-regulated kinase 1/2 and p38-mitogen-activated protein kinase, which is consistent with the findings reported for human neutrophils. Next, whether TLR2 participated in HP-NAP-induced secretion of interleukin-8 (IL-8) was investigated in neutrophils and ATRA-induced differentiated HL-60 cells. In both cells, TLR2 participated in HP-NAP-induced IL-8 secretion but not HP-NAP-induced ROS production. Interestingly, PTX-sensitive G proteins also contributed to the HP-NAP-induced secretion of IL-8 from neutrophils and the differentiated HL-60 cells. Our ELISA-based binding assay further revealed the competitive binding of Pam(3)CSK(4), a TLR2 agonist, and HP-NAP to TLR2, which suggests the presence of specific and direct interactions between HP-NAP and TLR2. Thus, HP-NAP directly interacts with and activates TLR2 to induce IL-8 secretion in neutrophils and ATRA-induced differentiated HL-60 cells.
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