Dopamine by itself activates either D2, D3 or D1/D5 dopaminergic receptors in normal human T-cells and triggers the selective secretion of either IL-10, TNFalpha or both.
The neurotransmitter dopamine on its own increased significantly TNFalpha and IL-10 secretion by resting normal-human T-cells, and induced approximately 5-fold elevation of the corresponding mRNA's, without affecting IFNgamma and IL-4. Using seven highly selective dopamine-receptor (DR) agonists and antagonists we found that TNFalpha-upregulation, evident after 24 h, was mediated by D3R and D1/D5R while IL-10-upregulation, evident after 72 h, was mediated by D2R and D1/D5R. We confirmed the expression of D2R and D3R in these human T cells. Dopamine's unique ability to trigger a selective secretion of either TNFalpha only (via D3R) or IL-10 only (via D2R) or both (via D1/D5R), differs from the robust and non-selective cytokine-secretion induced by 'classical' TCR-activation, and as such may have important beneficial or detrimental implications in various immunological and neurological diseases/injuries/cancers.
Besser
Michal J
MJ
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Ganor
Yonatan
Y
Levite
Mia
M
D015152:Blotting, Northern / Q000379:methods; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011954:Receptors, Dopamine / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004298:Dopamine