Adenosine inhibition of lipopolysaccharide-induced interleukin-6 secretion by the osteoblastic cell line MG-63

Joseph M. Russell, Graham S. Stephenson, Clare E Yellowley-genetos, Hilary P. Benton

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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, A2a, A2b, 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, A2a, and A2b 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 ADORA2a-specific antagonist ZM241385 partially reversed the inhibitory effects of ADORA stimulation on LPS-induced IL-6 release. Overall, these data suggest that ADORA2a 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.

Original languageEnglish (US)
Pages (from-to)316-326
Number of pages11
JournalCalcified Tissue International
Volume81
Issue number4
DOIs
StatePublished - Oct 2007

Keywords

  • Adenosine
  • Inflammation
  • Interleukin-6
  • Osteoblast
  • Purine receptor

ASJC Scopus subject areas

  • Endocrinology

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