Adenosine A2A receptor activation and macrophage-mediated experimental glomerulonephritis

Gabriela E. Garcia, Luan Truong, Ping Li, Ping Zhang, Jie Du, Jiang Fan Chen, Lili Feng

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A2A adenosine receptors (A2ARs) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine if selective activation of A 2AR would suppress inflammation in a rat model of glomerulonephritis. Activation of A2AR reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1α/CCL3, RANTES/CCL5, MIP-1β/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, interluekin (IL)-4 and IL-10, also increased. The mechanism for these anti-inflammatory responses to the A2AR agonist was suppression of macrophages function. A2AR expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A2AR agonist, and chemokines not expressed in macrophages did not respond to A 2AR activation. Thus, activation of the A2AR on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A2AR activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A2AR could be developed into a novel treatment for glomerulonephritis and other macrophage-related inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalFASEB Journal
Volume22
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Anti-inflammatory cytokines
  • Chemokines
  • Tissue injury protection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

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