Immunoregulation of IL-6 secretion by endogenous and exogenous adenosine and by exogenous purinergic agonists in splenic tissue slices.
In recent years, the role of norepinephrine, opioids, and neuropeptide Y for sympathetic regulation of murine spleen cells has been characterised. In this study, we describe the role of exogenous and endogenous adenosine and exogenous P2X(1) and P2Y(1) agonists for spontaneous splenic IL-6 secretion from spleen slices. The P2X(1) agonist beta,gamma-methylene ATP inhibited IL-6 secretion at 10(-5) M, whereas the P2Y(1) agonist 2-methylthio ATP increased IL-6 secretion at 10(-6) to 10(-8) M. Furthermore, adenosine (at 5 x 10(-8), 10(-7), 5 x 10(-7) M) inhibited IL-6 secretion via A1 adenosine receptors, whereas an A2(A) adenosine receptor agonist increased IL-6 secretion in the presence of 10(-7) M cortisol. To determine the effects of endogenous adenosine, electrical field stimulation was applied in order to release endogenous ATP, which yields adenosine after conversion from ATP. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the A1 antagonist DPCPX but not by the A2 antagonist 8-(3-Chlorostyryl)caffeine. Thus, via A1 adenosine receptors, adenosine was found to be a strong inhibitor of splenic IL-6 secretion. This study further expands our earlier description of the complexity of the local dialogue of sympathetic nerves and macrophages in lymphoid organs.
Straub
Rainer H
RH
Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
Pongratz
Georg
G
Günzler
Christian
C
Michna
Andreas
A
Baier
Simone
S
Kees
Frieder
F
Falk
Werner
W
Schölmerich
Jürgen
J
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D009638:Norepinephrine / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000294:innervation; D013564:Sympathetic Nervous System / Q000276:immunology; D013873:Thionucleotides / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D015850:Interleukin-6; C546383:P2ry1 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C081320:8-(3-chlorostyryl)caffeine; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D002110:Caffeine; D000255:Adenosine Triphosphate; D009638:Norepinephrine; C008501:2-methylthio-ATP