Inhibition by dexamethasone of antigen-induced c-Jun N-terminal kinase activation in rat basophilic leukemia cells

Noriyasu Hirasawa, Yukako Sato, Yuhko Fujita, Suetsugu Mue, Kazuo Ohuchi

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Antigen stimulation of IgE-sensitized rat basophilic leukemia RBL-2H3 cells induced activation of c-Jun N-terminal kinase (JNK) within a few minutes with maximum activity attained 40 min later. The increase in JNK activity was accompanied with an increase in phosphorylation of c-Jun in the cells. The Ag-induced JNK activation was inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin (10-100 nM) and LY 294002 (100 μM) but not by the protein kinase C inhibitors calphostin C (1 and 3 μM) and Ro 31-8425 (1 and 3 μM). Pretreatment with dexamethasone (10 and 100 nM) for 18 h inhibited the Ag-induced increase in JNK activity in a concentration-dependent manner. At least 6 h of preincubation with dexamethasone was necessary to inhibit the Ag-induced JNK activation. The phosphorylation of c-Jun induced by the Ag stimulation was reduced by pretreatment with dexamethasone without reduction of the content of c-Jun protein. The Ag-induced activation of the JNK kinase kinase mitogen- activated protein kinase-extracellular signal-regulated kinase kinase-1 was also inhibited by pretreatment with dexamethasone at 10 and 100 nM. These findings indicate that dexamethasone reduces JNK protein level and inhibits the Ag-induced activation of JNK resulting in the inhibition of c-Jun phosphorylation.

Original languageEnglish
Pages (from-to)4939-4943
Number of pages5
JournalJournal of Immunology
Volume161
Issue number9
Publication statusPublished - 1998 Nov 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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