Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in primary mouse CD4 T cells.
Vasoactive intestinal peptide receptor-1 (VPAC-1) is an anti-proliferative, G-protein coupled receptor that is highly expressed on naïve T cells, and has been reported to be downregulated upon T cell activation. The T cell signaling molecules involved in mediating low VPAC-1 levels have not been identified. Therefore, to gain a greater understanding into this regulation, this study investigated the signaling pathways that regulate (VPAC-1) in murine, primary CD4 T cells. To this end, murine, splenic CD4 T cells were pretreated separately with 10 different pharmacological inhibitors and incubated +/- anti-CD3 for 24h. Total RNA was isolated, and VPAC-1 mRNA levels were measured by qPCR. Our results support that JNK kinases, downstream from the protein kinase, Zap70, are involved in suppressive regulation of VPAC-1 steady-state mRNA levels after anti-CD3 treatment. In contrast, inhibitors against PKC, ERK, p38, Zap70 and Rac1 supported a stimulatory influence in VPAC-1 regulation in the absence of T cell signaling. By studying the signaling pathways that regulate VPAC-1 in T cells, we can gain greater insight into the role of this anti-inflammatory receptor in autoimmunity and infectious diseases.
Vomhof-DeKrey
Emilie E
EE
Department of Chemistry and Molecular Biology, The Center for Protease Research, North Dakota State University, Room 320 IACC Building, 1320 Albrecht Boulevard, Fargo, ND 58105, USA.
Dorsam
Glenn Paul
GP
Department of Chemistry and Molecular Biology, The Center for Protease Research, North Dakota State University, Room 320 IACC Building, 1320 Albrecht Boulevard, Fargo, ND 58105, USA. Electronic address: glenn.dorsam@ndsu.edu.
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019311:Staurosporine