Involvement of protein tyrosine kinases in il-2-induced activation of human monocytes

M. C. Bosco, A. Zea, T. Rowe, J. Ortaldo, L. Varesio, I. Espinoza-Delgado

Research output: Contribution to journalArticle

Abstract

The activating properties of interleukin-2 (IL-2) and the composition of the IL-2 receptor on human monocytes are well characterized. However, little is known on IL-2 post-binding events. In the present study, we investigated the role of protein tyrosine kinases (PTK) in the activation of human monocytes by IL-2. Induction of monocyte tumoricidal activity by IL-2 was suppressed, in a dose-dependent manner, by the PTK inhibitor herbimycin A Herbimycin A inhibitory activity was rather potent, because a concentration as low as 0.05 μM was sufficient to cause an almost complete suppression of IL-2-activated monocyte cytotoxicity. This effect was selective for IL-2, because the same dose of herbimycin A did not affect IFNγ-dependent cytotoxicity. Furthermore, incubation of monocytes with herbimycin A at 0.05 μM almost completely blocked the secretion of EL-1 β, TNFα, and IL-6, and significantly reduced IL-8 release from IL-2-stimulated monocytes. Finally, antiphosphotyrosine immunoblotting demonstrated that stimulation of monocytes with IL-2 for 30 min resulted in increased tyrosine phosphorylation of several proteins of molecular weights ranging from 40 to 140 kDa. These data strongly suggest that PTK activity is required for the direct activation of monocyte effector and secretory functions by IL-2.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number6
Publication statusPublished - 1996

Fingerprint

protein-tyrosine kinases
interleukin-2
monocytes
Protein-Tyrosine Kinases
Interleukin-2
Monocytes
Chemical activation
Cytotoxicity
cytotoxicity
Phosphorylation
Interleukin-2 Receptors
Protein Kinase Inhibitors
protein phosphorylation
Interleukin-8
interleukin-8
Immunoblotting
dosage
immunoblotting
Tyrosine
interleukin-6

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Involvement of protein tyrosine kinases in il-2-induced activation of human monocytes. / Bosco, M. C.; Zea, A.; Rowe, T.; Ortaldo, J.; Varesio, L.; Espinoza-Delgado, I.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Bosco, M. C. ; Zea, A. ; Rowe, T. ; Ortaldo, J. ; Varesio, L. ; Espinoza-Delgado, I. / Involvement of protein tyrosine kinases in il-2-induced activation of human monocytes. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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AU - Varesio, L.

AU - Espinoza-Delgado, I.

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