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Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells.
J Biol Chem 2001; 276(48):44856-64JB

Abstract

NF-kappaB is a critical regulator of genes involved in inflammation. Gastric epithelial cells and macrophages are considered the main sources of pro-inflammatory cytokines. We investigated NF-kappaB activation by Helicobacter pylori in MKN45 gastric epithelial cells and THP-1 monocytic cells. Although, cag pathogenicity island (PAI)-positive H. pylori (wild type) activated NF-kappaB in both cells, isogenic mutant of cagE (DeltacagE) activated it only in THP-1 cells. Supernatant from the wild type culture could activate NF-kappaB in THP-1 cells but not in MKN45 cells. High density cDNA array analysis revealed that mRNA expression of NF-kappaB-regulated genes such as interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha), and IL-1beta was significantly up-regulated by the wild type in both cells, whereas it was up-regulated by DeltacagE only in THP-1 cells. Experiments using CD14-neutralizing antibody and IL-1 receptor-associated kinase (IRAK) assay showed that both wild type and DeltacagE H. pylori activated NF-kappaB through CD14 and IRAK in THP-1 cells but not in MKN45 cells. Macrophages from C3H/HeJ mice carrying point mutation in the Toll-like receptor 4 (TLR4) gene showed decreased NF-kappaB activation and TNFalpha secretion compared with C3H/HeN mouse macrophage when treated with H. pylori. In conclusion, H. pylori-induced NF-kappaB activation in epithelial cells is dependent on cag PAI and contact but does not involve CD14 and IRAK, whereas in macrophage/monocytic cells it is independent of cag PAI or contact but involves CD14 and TLR4.

Authors+Show Affiliations

Department of Gastroenterology, Faculty of Medicine, University of Tokyo. 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. MAEDA-2IM@h.u-tokyo.ac.jpNo affiliation info availableNo affiliation info availableNo 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

11546774

Citation

Maeda, S, et al. "Distinct Mechanism of Helicobacter Pylori-mediated NF-kappa B Activation Between Gastric Cancer Cells and Monocytic Cells." The Journal of Biological Chemistry, vol. 276, no. 48, 2001, pp. 44856-64.
Maeda S, Akanuma M, Mitsuno Y, et al. Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. J Biol Chem. 2001;276(48):44856-64.
Maeda, S., Akanuma, M., Mitsuno, Y., Hirata, Y., Ogura, K., Yoshida, H., ... Omata, M. (2001). Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. The Journal of Biological Chemistry, 276(48), pp. 44856-64.
Maeda S, et al. Distinct Mechanism of Helicobacter Pylori-mediated NF-kappa B Activation Between Gastric Cancer Cells and Monocytic Cells. J Biol Chem. 2001 Nov 30;276(48):44856-64. PubMed PMID: 11546774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. AU - Maeda,S, AU - Akanuma,M, AU - Mitsuno,Y, AU - Hirata,Y, AU - Ogura,K, AU - Yoshida,H, AU - Shiratori,Y, AU - Omata,M, Y1 - 2001/08/23/ PY - 2001/9/8/pubmed PY - 2002/1/11/medline PY - 2001/9/8/entrez SP - 44856 EP - 64 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 276 IS - 48 N2 - NF-kappaB is a critical regulator of genes involved in inflammation. Gastric epithelial cells and macrophages are considered the main sources of pro-inflammatory cytokines. We investigated NF-kappaB activation by Helicobacter pylori in MKN45 gastric epithelial cells and THP-1 monocytic cells. Although, cag pathogenicity island (PAI)-positive H. pylori (wild type) activated NF-kappaB in both cells, isogenic mutant of cagE (DeltacagE) activated it only in THP-1 cells. Supernatant from the wild type culture could activate NF-kappaB in THP-1 cells but not in MKN45 cells. High density cDNA array analysis revealed that mRNA expression of NF-kappaB-regulated genes such as interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha), and IL-1beta was significantly up-regulated by the wild type in both cells, whereas it was up-regulated by DeltacagE only in THP-1 cells. Experiments using CD14-neutralizing antibody and IL-1 receptor-associated kinase (IRAK) assay showed that both wild type and DeltacagE H. pylori activated NF-kappaB through CD14 and IRAK in THP-1 cells but not in MKN45 cells. Macrophages from C3H/HeJ mice carrying point mutation in the Toll-like receptor 4 (TLR4) gene showed decreased NF-kappaB activation and TNFalpha secretion compared with C3H/HeN mouse macrophage when treated with H. pylori. In conclusion, H. pylori-induced NF-kappaB activation in epithelial cells is dependent on cag PAI and contact but does not involve CD14 and IRAK, whereas in macrophage/monocytic cells it is independent of cag PAI or contact but involves CD14 and TLR4. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11546774/Distinct_mechanism_of_Helicobacter_pylori_mediated_NF_kappa_B_activation_between_gastric_cancer_cells_and_monocytic_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11546774 DB - PRIME DP - Unbound Medicine ER -