Strathprints logo
Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

Verotoxin activates mitogen-activated protein kinase in human peripheral blood monocytes: role in apoptosis and proinflammatory cytokine release

Cameron, P. and Smith, S.J. and Giembycz, M.A. and Rotondo, D. and Plevin, R.J. (2003) Verotoxin activates mitogen-activated protein kinase in human peripheral blood monocytes: role in apoptosis and proinflammatory cytokine release. British Journal of Pharmacology, 140 (7). pp. 1320-1330. ISSN 0007-1188

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

In this study, we examined the role of mitogen-activated protein (MAP) kinases in the effects of verotoxins (VTs), from Escherichia coli O157:H7, upon both apoptosis and the release of tumour necrosis factor alpha (TNF-α) and granulocyte–macrophage colony-stimulated factor (GM-CSF) from human monocytes. Both VT1 and VT2 stimulated a weak, transient increase in c-Jun-N-terminal kinase (JNK) activity and a strong activation of both p38 mitogen-activated protein kinase (MAP kinase) and extracellular-regulated kinase (ERK) activity in human monocytes, which was sustained in the case of p38 MAP kinase. Stimulation of human monocytes with VT2 (100 ng ml−1) did not result in an increase in apoptosis; however, the toxin stimulated the release of both TNF-α and GM-CSF. Pretreatment of human monocytes with the p38 MAP kinase inhibitor SB203580, at concentrations from 100 nm to 10 μm, significantly decreased the VT1- and VT2-induced TNF-α and GM-CSF release from monocytes. In contrast, inhibition of MEK1 with PD98059 only significantly decreased GM-CSF release. Pretreatment of monocytes with SP600125 inhibited both GM-CSF and TNF-α production; however, significant effects upon p38 MAP kinase and ERK activation were observed. Taken together, these results suggest a role for p38 MAP kinase and ERK in cytokine generation in response to the verotoxins. A role for JNK remains undetermined.

Item type: Article
ID code: 37889
Keywords: e. coli O157, apoptosis , verotoxins , c-Jun-N-terminal kinase, p38 MAP kinase, protein kinase, Pharmacy and materia medica, Pharmacology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 24 Feb 2012 16:55
    Last modified: 04 Sep 2014 19:15
    URI: http://strathprints.strath.ac.uk/id/eprint/37889

    Actions (login required)

    View Item