Trypanosoma cruizi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells

Shankar Mukherjee, Huan Huang, Stefka B. Petkova, Chris Albanese, Richard G. Pestell, Vicki L. Braunstein, George J. Christ, Murray Wittner, Michael P. Lisanti, Joan W. Berman, Louis M. Weiss, Herbert B. Tanowitz

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Abstract

Trypanosoma cruzi infection causes cardiomyopathy and vasculopathy. We examined the consequence of this infection for the mitogen-activated protein kinase (MAPK) pathways, which regelate cell proliferation in cultured human umbilical vein endothelial and vascular smooth muscle cells. Infection of these cells resulted in activation of extracellular signal-regulated kinases land 2 (ERK1/2) but not c-Jun N-terminal kinase or p38 MAPK. Treatment of these cells with the MAPK kinase inhibitor PD98059 prior to infection blocked the increase in phosphorylated ERK1/2 seen with infection. Heat-killed parasites did not activate ERK1/2, indicating that activation of ERK1/2 was dependent on infection of these cells by live parasites. Furthermore, transfection with dominant-negative Raf(301) or Ras(N17) constructs reduced the infection-associated levels of phospho-ERK1/2, indicating that the activation of ERK1/2 involved the Ras-Raf-ERK pathway. Infection also resulted in an increase in activator protein 1 (AP-1) activity, which was inhibited by transfection with a dominant-negative Raf(301) construct. T. cruzi-infected endothelial cells secreted endothelin-1 and interleukin-1β, which activated ERK1/2 and induced cyclin D1 expression in uninfected smooth muscle cells. These data suggest a possible molecular paradigm for the pathogenesis of the vasculopathy and the cardiovascular remodeling associated with T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)5274-5282
Number of pages9
JournalInfection and Immunity
Volume72
Issue number9
DOIs
StatePublished - Sep 2004

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Trypanosoma
Extracellular Signal-Regulated MAP Kinases
Smooth Muscle Myocytes
Infection
Trypanosoma cruzi
Transfection
Parasites
Mitogen-Activated Protein Kinase 9
Umbilical Veins
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
Cyclin D1
Mitogen-Activated Protein Kinase Kinases
Transcription Factor AP-1
Endothelin-1
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Cardiomyopathies
Interleukin-1
Vascular Smooth Muscle

ASJC Scopus subject areas

  • Immunology

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Trypanosoma cruizi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells. / Mukherjee, Shankar; Huang, Huan; Petkova, Stefka B.; Albanese, Chris; Pestell, Richard G.; Braunstein, Vicki L.; Christ, George J.; Wittner, Murray; Lisanti, Michael P.; Berman, Joan W.; Weiss, Louis M.; Tanowitz, Herbert B.

In: Infection and Immunity, Vol. 72, No. 9, 09.2004, p. 5274-5282.

Research output: Contribution to journalArticle

Mukherjee, S, Huang, H, Petkova, SB, Albanese, C, Pestell, RG, Braunstein, VL, Christ, GJ, Wittner, M, Lisanti, MP, Berman, JW, Weiss, LM & Tanowitz, HB 2004, 'Trypanosoma cruizi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells', Infection and Immunity, vol. 72, no. 9, pp. 5274-5282. https://doi.org/10.1128/IAI.72.9.5274-5282.2004
Mukherjee, Shankar ; Huang, Huan ; Petkova, Stefka B. ; Albanese, Chris ; Pestell, Richard G. ; Braunstein, Vicki L. ; Christ, George J. ; Wittner, Murray ; Lisanti, Michael P. ; Berman, Joan W. ; Weiss, Louis M. ; Tanowitz, Herbert B. / Trypanosoma cruizi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells. In: Infection and Immunity. 2004 ; Vol. 72, No. 9. pp. 5274-5282.
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