Expression of functional kappa-opioid receptors on murine dendritic cells.
Endogenous and exogenous opioids are known to exert direct effects on the immune system and the expression of functional opioid receptors has been reported for several immune cell types. Since dendritic cells are important inducers and regulators of immune responses, we investigated whether murine dendritic cells express functional kappa-opioid receptors. FACScan analysis and radioligand binding studies revealed the expression of kappa-opioid receptors by murine dendritic cells, which by RT-PCR were also shown to express kappa-opioid mRNA. In a primary allogenic mixed-lymphocyte reaction the kappa-agonists dynorphin A and U50488H suppressed the capacity of dendritic cells to induce T-cell proliferation in a concentration-dependent manner. Preincubation with the kappa-specific antagonist nor-binaltrophimine abolished the observed effect, indicating specificity. In contrast, antigen uptake by dendritic cells as well as phenotypic maturation of dendritic cells were not influenced by the kappa-agonists dynorphin A and U50488H. In summary our data demonstrate that dendritic cells express functional kappa-opioid receptors and that specific agonists exert a direct effect on these cells. Therefore, dendritic cells might be involved in the interaction of the neuroendocrine hormones and the immune system.
Kirst
Annette
A
Institute of Pharmacology and Toxicology, Julius-Maximilians-University, Versbacher Strasse 9, D-97078, Wurzburg, Germany.
Wack
Christiane
C
Lutz
Werner K
WK
Eggert
Andreas
A
Kämpgen
Eckart
E
Fischer
Wolfgang H
WH
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004399:Dynorphins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins