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Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells.

Publication ,  Journal Article
Reinstein, LJ; Lichtman, SN; Currin, RT; Wang, J; Thurman, RG; Lemasters, JJ
Published in: Hepatology
June 1994

In liver grafts that will fail as a result of storage injury, reperfusion activates Kupffer cells. Overproduction of tumor necrosis factor by activated Kupffer cells may cause primary graft nonfunction, multiple organ failure and, eventually, death of graft recipients. Carolina rinse solution, adenosine, nisoldipine, pentoxifylline and prostaglandin E1 reduce graft failure from storage/reperfusion injury. To test the hypothesis that these agents act by suppressing cytokine release by activated Kupffer cells, we assessed the effect of each drug on tumor necrosis factor released from cultured rat Kupffer cells stimulated with lipopolysaccharide. Adenosine, nisoldipine and prostaglandin E1 each suppressed lipopolysaccharide-stimulated tumor necrosis factor release. The adenosine A2 receptor agonists. 5-n-ethylcarboxamidadenosine, 2-chloro-adenosine and R-phenylisopropyl adenosine also blocked tumor necrosis factor release in a potency suggestive of A2 receptor activity. Xanthine amine congener, a specific A1 receptor antagonist, failed to reverse the suppression by adenosine of tumor necrosis factor release, whereas CGS15943A, an A2 receptor antagonist, did reverse suppression by adenosine and 5-n-ethylcarboxamidadenosine. CGS15943A had no effect on suppression of lipopolysaccharide-stimulated tumor necrosis factor release by nisoldipine or prostaglandin E1. Dibutyryl-cyclicAMP also suppressed tumor necrosis factor release. Adenosine, 5-n-ethylcarboxamidadenosine, prostaglandin E1 and pentoxifylline increased cyclicAMP levels in cultured Kupffer cells, but nisoldipine did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

Hepatology

ISSN

0270-9139

Publication Date

June 1994

Volume

19

Issue

6

Start / End Page

1445 / 1452

Location

United States

Related Subject Headings

  • Xanthines
  • Tumor Necrosis Factor-alpha
  • Triazoles
  • Receptors, Purinergic P1
  • Rats, Sprague-Dawley
  • Rats
  • Quinazolines
  • Nisoldipine
  • Lipopolysaccharides
  • Kupffer Cells
 

Citation

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ICMJE
MLA
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Reinstein, L. J., Lichtman, S. N., Currin, R. T., Wang, J., Thurman, R. G., & Lemasters, J. J. (1994). Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells. Hepatology, 19(6), 1445–1452.
Reinstein, L. J., S. N. Lichtman, R. T. Currin, J. Wang, R. G. Thurman, and J. J. Lemasters. “Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells.Hepatology 19, no. 6 (June 1994): 1445–52.
Reinstein LJ, Lichtman SN, Currin RT, Wang J, Thurman RG, Lemasters JJ. Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells. Hepatology. 1994 Jun;19(6):1445–52.
Reinstein LJ, Lichtman SN, Currin RT, Wang J, Thurman RG, Lemasters JJ. Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells. Hepatology. 1994 Jun;19(6):1445–1452.
Journal cover image

Published In

Hepatology

ISSN

0270-9139

Publication Date

June 1994

Volume

19

Issue

6

Start / End Page

1445 / 1452

Location

United States

Related Subject Headings

  • Xanthines
  • Tumor Necrosis Factor-alpha
  • Triazoles
  • Receptors, Purinergic P1
  • Rats, Sprague-Dawley
  • Rats
  • Quinazolines
  • Nisoldipine
  • Lipopolysaccharides
  • Kupffer Cells