Upregulation of A_2A adenosine receptor expression by TNF-α in PBMC of patients with CHF: a regulatory mechanism of inflammation

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• 作者：Pier leopoldo Capecchi ; Aless ; ra Camurri ; Gerarda Pompella ; Alessia Mazzola ; Massimo Maccherini ; Francesco Diciolla ; Pietro enea Lazzerini ; Maria P. Abbracchio ; Franco Laghi-Pasini
• 关键词：Adenosine receptors ; cardiac failure ; monocytes ; TNF-α
• 刊名：Journal of Cardiac Failure
• 出版年：2005
• 出版时间：February 2005
• 年：2005
• 卷：11
• 期：1
• 页码：67-73
• 全文大小：210 K

文摘

Tumor necrosis factor (TNF)-α plays a role in congestive heart failure (CHF). A_2A adenosine receptor (A_2AR) activation on immune cells putatively reduces the release of cytokines contributing to CHF progression. The study is aimed at determining the role of the A_2AR in the modulation of TNF-α production, and the ex vivo effect of TNF-α on A_2AR in peripheral blood mononuclear cells (PBMC) from CHF patients.

Methods and results

Plasma levels of TNF-α and TNF-α production from lipopolysaccharide (LPS)-stimulated PBMC were evaluated in 26 CHF patients in comparison to controls. The effects of the A_2AR agonist CGS-21680 and antagonist ZM-241385 on TNF-α production from PBMC were also evaluated. Finally, reverse transcriptase-polymerase chain reaction and Western blot analyses of A_2AR in PBMC were performed in TNF-α–treated and untreated cells. TNF-α production from LPS-stimulated PBMC was enhanced in CHF patients with respect to controls. CGS-21680 blunted TNF-α production in both groups; ZM-241385 reverted this effect. A_2AR expression in PBMC was higher in CHF patients than in controls. TNF-α addition produced an increase in A_2AR in PBMC from controls but not in PBMC from CHF patients.

Conclusions

PBMC from CHF patients show an upregulation of A_2AR-mediated inhibition of TNF-α, which may represents a mechanism of protection against inappropriate cytokine production.