Adenosine inhibition of lipopolysaccharide-induced interleukin-6 secretion by the osteoblastic cell line MG-63.
Adenosine is known to inhibit inflammatory responses in many cell systems via a family of purine receptors termed "P1." The P1 family consists of the adenosine receptors (ADORA) of subtypes A(1), A(2a), A(2b), and A(3). In order to assess whether adenosine has anti-inflammatory actions in osteoblastic cells, we investigated its effects on lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in an in vitro inflammatory functional response model. We showed that the osteoblastic cell line MG-63 expresses ADORA(1), A(2a), and A(2b) but not A(3). Treatment of MG-63 cells with adenosine and pharmacological ADORA agonist 5'-N-ethylcarboxamidoadenosine or 2-[4-(2-p-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) inhibits LPS-induced IL-6 release. This inhibition was protein kinase A (PKA)-dependent and mimicked by treatment with the adenylate cyclase activator forskolin. Treatment of MG-63 with the ADORA(2a)-specific antagonist ZM241385 partially reversed the inhibitory effects of ADORA stimulation on LPS-induced IL-6 release. Overall, these data suggest that ADORA(2a) is involved in the regulation of LPS-induced IL-6 release, thus illustrating a regulatory role for adenosine receptors in the control of inflammation and potentially osteoclastogenesis and bone resorption.
Russell
Joseph M
JM
Department of Veterinary Medicine, Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA. jmrussell@ucdavis.edu
Stephenson
Graham S
GS
Yellowley
Clare E
CE
Benton
Hilary P
HP
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma / Q000473:pathology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D013997:Time Factors; D000093242:Interleukin-6 Inhibitors
D000241:Adenosine; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D015850:Interleukin-6; D008070:Lipopolysaccharides; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000093242:Interleukin-6 Inhibitors