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

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

Title	en Extracellular signal regulated protein kinase and c-jun N-terminal kinase are involved in ml muscarinic receptor-enhanced interleukin-2 production pathway in Jurkat cells.
Creator	en Fujino, Hiromichi en Uehara, Takashi en Murayama, Toshihiko en Okuma, Yasunobu en Ariga, Hiroyoshi NRID 1000020143505 en Nomura, Yasuyuki
Accessrights	open access
Subject	Other en muscarinic receptor Other en interleukin-2 Other en neuroimmune interaction Other en Jurkat cell MeSH en Blotting, Western MeSH en Cells, Cultured MeSH en Enzyme-Linked Immunosorbent Assay MeSH en Humans MeSH en Interleukin-2/biosynthesis MeSH en JNK Mitogen-Activated Protein Kinases MeSH en Jurkat Cells MeSH en Luciferases/metabolism MeSH en Mitogen-Activated Protein Kinase 1/metabolism MeSH en Mitogen-Activated Protein Kinases/metabolism MeSH en RNA/biosynthesis MeSH en RNA/isolation & purification MeSH en Receptor, Muscarinic M1 MeSH en Receptors, Muscarinic/metabolism MeSH en Reverse Transcriptase Polymerase Chain Reaction MeSH en Transfection NDC 499
Description	Abstract en 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 ml/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 ml and m2 muscarinic receptors exist on Jurkat cells. The stimulation of ml 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 ml receptors did not modify the DNA binding of NF-kappaB, NF-AT or Oct-1. When ml 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 [Ca2+]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 ml receptor stimulation. The results suggest that transcription factor AP-1 is involved in the ml 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 ml receptor-mediated enhancement of IL-2 promoter activity.
Publisher	en The Pharmaceutical Society of Japan
Date	Issued2000-10
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/53969
Relation	isIdenticalTo DOI https://doi.org/10.1248/bpb.23.1198 PMID 11041251
Journal	PISSN 0918-6158 en Biological & pharmaceutical bulletin Volume Number23 Issue Number10 Page Start1198 Page End1205
File	fulltext 108_Ariga_2000_Biol_Pharm_Bull.pdf 1.46 MB (application/pdf) Issued2000-10
Oaidate	2023-07-26