Acute IL-3 priming up-regulates the stimulus-induced Raf-1-Mek-Erk cascade independently of IL-3-induced activation of Erk

Natalia Vilariño, Katsushi Miura, Donald Macglashan

Research output: Contribution to journalArticle

Abstract

IL-3 is a potent priming cytokine for human basophils, inducing an increase of mediator release after stimulation. The mechanism of IL-3 priming of the basophil response to FcεRI aggregating stimuli remains unknown. We explored the regulation of several elements of IgE-mediated signaling by a short priming with IL-3. Early signaling events such as phosphorylation of Syk, Shc, linker for activation of T cells, and the calcium signal were not statistically affected by acute IL-3 priming. Downstream in the signaling cascade, a point of up-regulation was found at the level of Raf-1-Mek-Erk. Although the phosphorylation of Raf-1 was not changed by IL-3 priming, IL-3-primed anti-IgE-stimulated basophils showed a strong synergism for Mek and Erk phosphorylation when compared with either IL-3 or anti-IgE alone; pre-exposure to IL-3 induced a final 13-fold average increase over anti-IgE-induced Erk phosphorylation (6-fold above the sum of anti-IgE and IL-3 alone). The kinetics, dose response, and pharmacologic characteristics of the EL-3 priming of stimulus-induced Erk phosphorylation support the involvement of a yet unknown mechanism that is independent of IL-3-induced Erk and PI3K activation. This type of preactivation can be mimicked by incubation with the Ser-Thr kinase inhibitors, Ro-81-3220, or bisindoylmaleimide II.

Original languageEnglish (US)
Pages (from-to)3006-3014
Number of pages9
JournalJournal of Immunology
Volume175
Issue number5
StatePublished - Sep 1 2005

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Interleukin-3
Up-Regulation
Phosphorylation
Basophils
Phosphatidylinositol 3-Kinases
Immunoglobulin E
Phosphotransferases
Cytokines
Calcium
T-Lymphocytes
anti-IgE antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Acute IL-3 priming up-regulates the stimulus-induced Raf-1-Mek-Erk cascade independently of IL-3-induced activation of Erk. / Vilariño, Natalia; Miura, Katsushi; Macglashan, Donald.

In: Journal of Immunology, Vol. 175, No. 5, 01.09.2005, p. 3006-3014.

Research output: Contribution to journalArticle

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