Cl-IB-MECA enhances TNF-α release in peritoneal macrophages stimulated with LPS

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• 作者：Giovanni Forte^a ; Rosalinda Sorrentino^a ; Antonella Montinaro^a ; Aldo Pinto^a ; Silvana Morello ; ^a ; ^{smorello@unisa.it} ; ^{morello.silvana@gmail.com}
• 关键词：TNF-α ; Macrophages ; LPS ; Cl-IB-MECA
• 刊名：Cytokine
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：54
• 期：2
• 页码：161-166
• 全文大小：574 K

文摘

Adenosine receptor A3 (A3R) belongs to the Gi/Gq-coupled receptor family, that leads to the intracellular cAMP reduction and intracellular calcium increase, respectively. A3R is widely expressed and it can play a crucial role in many patho-physiological conditions, including inflammation. Here we investigate the effect of Cl-IB-MECA, A3R agonist, on the production of TNF-α. We found that Cl-IB-MECA enhances LPS-induced TNF-α release in peritoneal macrophages. This effect is reduced by MRS1191, A3R antagonist and by forskolin, activator of adenylyl cyclase. pIκBα increased in LPS + Cl-IB-MECA-treated macrophages, while total IκB kinase-β (IKKβ) reduced. Indeed, p65NF-κB nuclear translocation increased in cells treated with LPS + Cl-IB-MECA. Moreover, IMD 0354, IKKβ inhibitor, significantly abrogated the effect of Cl-IB-MECA on TNF-α release. Inhibition of protein kinase C (PKC) significantly reduced Cl-IB-MECA-induced TNF-α release in LPS-stimulated macrophages. Furthermore, LY-294002, PI3 K inhibitor, reduced the TNF-α production enhanced by Cl-IB-MECA, although the phosphorylation status of Akt did not change in cells treated with LPS + Cl-IB-MECA than LPS alone.

In summary, these data show that Cl-IB-MECA is able to enhance TNF-α production in LPS-treated macrophages in an NF-κB- dependent manner.