<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells

<i>Helicobacter pylori</i> 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 r...

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Autores principales:	Shao-Hsuan Wen, Zhi-Wei Hong, Chung-Chu Chen, Han-Wen Chang, Hua-Wen Fu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Helicobacter pylori</i> neutrophil-activating protein HP-NAP TLR2 HL-60 cells neutrophils IL-8 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5fd6f6d06efe425cac45af791694813b
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spelling	oai:doaj.org-article:5fd6f6d06efe425cac45af791694813b2021-11-11T17:02:48Z<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells10.3390/ijms2221115601422-00671661-6596https://doaj.org/article/5fd6f6d06efe425cac45af791694813b2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11560https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Helicobacter pylori</i> 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<sub>3</sub>CSK<sub>4</sub>, 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.Shao-Hsuan WenZhi-Wei HongChung-Chu ChenHan-Wen ChangHua-Wen FuMDPI AGarticle<i>Helicobacter pylori</i> neutrophil-activating proteinHP-NAPTLR2HL-60 cellsneutrophilsIL-8Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11560, p 11560 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Helicobacter pylori</i> neutrophil-activating protein HP-NAP TLR2 HL-60 cells neutrophils IL-8 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Helicobacter pylori</i> neutrophil-activating protein HP-NAP TLR2 HL-60 cells neutrophils IL-8 Biology (General) QH301-705.5 Chemistry QD1-999 Shao-Hsuan Wen Zhi-Wei Hong Chung-Chu Chen Han-Wen Chang Hua-Wen Fu <i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
description	<i>Helicobacter pylori</i> 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<sub>3</sub>CSK<sub>4</sub>, 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.
format	article
author	Shao-Hsuan Wen Zhi-Wei Hong Chung-Chu Chen Han-Wen Chang Hua-Wen Fu
author_facet	Shao-Hsuan Wen Zhi-Wei Hong Chung-Chu Chen Han-Wen Chang Hua-Wen Fu
author_sort	Shao-Hsuan Wen
title	<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
title_short	<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
title_full	<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
title_fullStr	<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
title_full_unstemmed	<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells
title_sort	<i>helicobacter pylori</i> neutrophil-activating protein directly interacts with and activates toll-like receptor 2 to induce the secretion of interleukin-8 from neutrophils and atra-induced differentiated hl-60 cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5fd6f6d06efe425cac45af791694813b
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<i>Helicobacter pylori</i> Neutrophil-Activating Protein Directly Interacts with and Activates Toll-like Receptor 2 to Induce the Secretion of Interleukin-8 from Neutrophils and ATRA-Induced Differentiated HL-60 Cells

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