Extracellular signal regulated protein kinase and c-Jun N-terminal kinase are involved in m1 muscarinic receptor-enhanced interleukin-2 production pathway in Jurkat cells

Hiromichi Fujino, Takashi Uehara, Toshihiko Murayama, Yasunobu Okuma, Hiroyoshi Ariga, Yasuyuki Nomura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We have previously shown that m1 and m2 muscarinic receptors were expressed on human peripheral blood lymphocytes (hPBL) and that pre-stimulation of these receptors enhanced phytohemagglutinin (PHA)-induced interleukin-2 (IL-2) production. Possible intracellular signal pathways of muscarinic receptors to regulate IL-2 production were examined in human T cell line Jurkat cells. Pretreatment of the cells with muscarinic receptor agonist, oxotremorine M (Oxo-M), enhanced IL-2 production induced by phorbol 12-myristate 13-acetate (PMA)/A23187, while Oxo-M by itself did not affect IL-2 production. The enhancement of IL-2 production by Oxo-M was inhibited by 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) an m1/m3 receptor antagonist. When the cells were pretreated with AF-DX116, an m2 antagonist, the IL-2 production enhanced by Oxo-M was further stimulated. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that m1 and m2 muscarinic receptors exist on Jurkat cells. The stimulation of m1 receptors enhanced the PMA/A23187-induced binding activity to AP-1 consensus sequences in IL-2 promoter and production of c-Fos and c-Jun protein. The stimulation of m1 receptors did not modify the DNA binding of NF-κB, NF-AT or Oct-1. When m1 receptors were stimulated, activities of mitogen activated protein kinase (MAPK)/extracellular signal regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were increased, while p38 MAPK was not affected. Incubation with Oxo-M induced a transient increase in [Ca 2+](i), which was abolished by pretreatment with 4-DAMP. Treatment with cyclosporin A markedly decreased the PMA/A23187-induced IL-2 promoter activity. This treatment, however, did not affect the enhancement of the promoter activity induced by m1 receptor stimulation. The results suggest that transcription factor AP-1 is involved in the m1 receptor-mediated enhancement of IL-2 transcript in Jurkat cells, and that pathways via MAPK/ERK and JNK, but not via p38 MAPK, are involved in the m1 receptor-mediated enhancement of IL-2 promoter activity.

Original languageEnglish
Pages (from-to)1198-1205
Number of pages8
JournalBiological and Pharmaceutical Bulletin
Volume23
Issue number10
Publication statusPublished - 2000
Externally publishedYes

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Muscarinic M1 Receptors
Jurkat Cells
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Protein Kinases
Interleukin-2
Calcimycin
Muscarinic M2 Receptors
Acetates
Transcription Factor AP-1
Muscarinic Receptors
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Proto-Oncogene Proteins c-jun
Muscarinic Agonists
Consensus Sequence
Phytohemagglutinins
Lymphocyte Activation
Cyclosporine
Reverse Transcription

Keywords

  • Interleukin-2
  • Jurkat cell
  • Muscarinic receptor
  • Neuroimmune interaction

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Extracellular signal regulated protein kinase and c-Jun N-terminal kinase are involved in m1 muscarinic receptor-enhanced interleukin-2 production pathway in Jurkat cells. / Fujino, Hiromichi; Uehara, Takashi; Murayama, Toshihiko; Okuma, Yasunobu; Ariga, Hiroyoshi; Nomura, Yasuyuki.

In: Biological and Pharmaceutical Bulletin, Vol. 23, No. 10, 2000, p. 1198-1205.

Research output: Contribution to journalArticle

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