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 A₁, A_2a, A_2b, and A₃. 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 ADORA₁, A_2a, and A_2b but not A₃. 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.