The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

Pazit Salamon, Irit Shefler, Alon Y. Hershko, Yoseph A. Mekori

Research output: Contribution to journalArticlepeer-review

Abstract

Background: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation. Methods: Human MC were stimulated by activated T cell membranes (T∗m). Phosphorylation of kinases was assessed by Western blotting. Protein kinase D (PKD) translocation was visualized by confocal microscopy. Degranulation was assessed by β-hexosaminidase release and cytokine production by ELISA. Results: Stimulation of human MC by activated T∗m resulted in the activation of PKD. PKD inhibition by the specific pharmacological inhibitor Gö6976 resulted in a reduction in the phosphorylation of p38 but not ERK. Gö6976 also inhibited degranulation and cytokine release. Conclusions: MC stimulation by physical contact with T cells results in PKD activation, leading to the phosphorylation of p38, degranulation and release of cytokines. Understanding the molecular events associated with T cell-induced MC activation might lead to therapeutic approaches for controlling T cell-mediated inflammatory processes in which MC participate.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalInternational Archives of Allergy and Immunology
Volume171
Issue number3-4
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

Keywords

  • Heterotypic adhesion
  • Mast cells
  • Protein kinase D
  • T cells

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