Tags

Type your tag names separated by a space and hit enter

Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages.
Biochem J. 2002 Nov 15; 368(Pt 1):121-9.BJ

Abstract

Gastric infection, as well as inflammation, caused by Helicobacter pylori, activates the production of cytokines and chemokines by mononuclear cells; interleukin-8 (IL-8) is one of the major inflammatory chemokines. Since H. pylori does not invade mucosal tissue, we observed the effect of the water extract of H. pylori (HPE), containing shed factors, on the production of IL-8 by human peripheral blood monocytes and the human monocyte cell line THP-1. HPE-treatment induced activation of the mitogen-activated protein kinases (MAPKs) ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase), an effect which was not dependent on the presence of the cag pathogenicity island. p38 MAPK activation was sustained. The specific inhibitors, U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling), both abrogated IL-8 secretion from HPE-treated THP-1. Dominant-negative mutants of the upstream kinases MEK1 (MAPK/ERK kinase 1), MKK (MAPK kinase) 6 and MKK7 also inhibited IL-8 secretion, pointing to a role of all three MAPKs in HPE-mediated IL-8 release. The inhibitory effects of polymyxin B and anti-CD14 antibody suggested that the effect of HPE on MAPKs was mediated by H. pylori lipopolysaccharide (LPS). By analysis of IL-8-promoter-driven luciferase gene expression, we observed that the effects of HPE-induced nuclear factor-kappaB (NF-kappaB) activation and MAPK signalling were mediated at the level of the IL-8 promoter. While ERK1/2 activation could be linked to enhanced DNA binding of activator protein-1 (AP-1), p38 MAPK signalling did not affect AP-1 DNA binding. Taken together, these results provide the first evidence that LPS from H. pylori stimulates IL-8 release from cells of the monocytic lineage through activation of NF-kappaB and signalling along MAPK cascades. The stimulation of MAPK signalling in macrophages by LPS of H. pylori amplifies the inflammatory response associated with gastric H. pylori infection and needs to be taken into consideration when developing therapeutics based on these signalling pathways.

Authors+Show Affiliations

Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road, Kolkata 700009, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12150710

Citation

Bhattacharyya, Asima, et al. "Mitogen-activated Protein Kinases and Nuclear factor-kappaB Regulate Helicobacter Pylori-mediated Interleukin-8 Release From Macrophages." The Biochemical Journal, vol. 368, no. Pt 1, 2002, pp. 121-9.
Bhattacharyya A, Pathak S, Datta S, et al. Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages. Biochem J. 2002;368(Pt 1):121-9.
Bhattacharyya, A., Pathak, S., Datta, S., Chattopadhyay, S., Basu, J., & Kundu, M. (2002). Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages. The Biochemical Journal, 368(Pt 1), 121-9.
Bhattacharyya A, et al. Mitogen-activated Protein Kinases and Nuclear factor-kappaB Regulate Helicobacter Pylori-mediated Interleukin-8 Release From Macrophages. Biochem J. 2002 Nov 15;368(Pt 1):121-9. PubMed PMID: 12150710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages. AU - Bhattacharyya,Asima, AU - Pathak,Shresh, AU - Datta,Simanti, AU - Chattopadhyay,Santanu, AU - Basu,Joyoti, AU - Kundu,Manikuntala, PY - 2002/08/01/accepted PY - 2002/07/23/revised PY - 2002/04/09/received PY - 2002/8/2/pubmed PY - 2002/12/28/medline PY - 2002/8/2/entrez SP - 121 EP - 9 JF - The Biochemical journal JO - Biochem J VL - 368 IS - Pt 1 N2 - Gastric infection, as well as inflammation, caused by Helicobacter pylori, activates the production of cytokines and chemokines by mononuclear cells; interleukin-8 (IL-8) is one of the major inflammatory chemokines. Since H. pylori does not invade mucosal tissue, we observed the effect of the water extract of H. pylori (HPE), containing shed factors, on the production of IL-8 by human peripheral blood monocytes and the human monocyte cell line THP-1. HPE-treatment induced activation of the mitogen-activated protein kinases (MAPKs) ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase), an effect which was not dependent on the presence of the cag pathogenicity island. p38 MAPK activation was sustained. The specific inhibitors, U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling), both abrogated IL-8 secretion from HPE-treated THP-1. Dominant-negative mutants of the upstream kinases MEK1 (MAPK/ERK kinase 1), MKK (MAPK kinase) 6 and MKK7 also inhibited IL-8 secretion, pointing to a role of all three MAPKs in HPE-mediated IL-8 release. The inhibitory effects of polymyxin B and anti-CD14 antibody suggested that the effect of HPE on MAPKs was mediated by H. pylori lipopolysaccharide (LPS). By analysis of IL-8-promoter-driven luciferase gene expression, we observed that the effects of HPE-induced nuclear factor-kappaB (NF-kappaB) activation and MAPK signalling were mediated at the level of the IL-8 promoter. While ERK1/2 activation could be linked to enhanced DNA binding of activator protein-1 (AP-1), p38 MAPK signalling did not affect AP-1 DNA binding. Taken together, these results provide the first evidence that LPS from H. pylori stimulates IL-8 release from cells of the monocytic lineage through activation of NF-kappaB and signalling along MAPK cascades. The stimulation of MAPK signalling in macrophages by LPS of H. pylori amplifies the inflammatory response associated with gastric H. pylori infection and needs to be taken into consideration when developing therapeutics based on these signalling pathways. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/12150710/Mitogen_activated_protein_kinases_and_nuclear_factor_kappaB_regulate_Helicobacter_pylori_mediated_interleukin_8_release_from_macrophages_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20020555 DB - PRIME DP - Unbound Medicine ER -