Characterisation of the prostaglandin E₂-ethanolamide suppression of tumour necrosis factor-¦Á production in human monocytic cells

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• 作者：Kirsten L. Brown ; Jillian Davidson ; Dino Rotondo ; ^{d.rotondo@strath.ac.uk}
• 关键词：Prostaglandin&ndash ; ethanolamide ; TNF-¦Á production ; Human immune cells ; Monocytes ; Inflammatory response
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：1831
• 期：6
• 页码：1098-1107
• 全文大小：1066 K

文摘

Background and purpose

Prostaglandin ethanolamides or prostamides are naturally occurring neutral lipid derivatives of prostaglandins that have been shown to be synthesised in vivo following COX-facilitated oxygenation of arachidonoyl ethanolamine (anandamide). Although the actions of prostaglandins have been extensively studied, little is known about the physiological or pathophysiological effects of prostamides. Since prostaglandin E₂ has potent immunosuppressive/immunomodulating actions, the aim of the present study was to determine whether the derivative, prostaglandin E₂ ethanolamide (PGE₂-EA), could modulate the production of the pro-inflammatory cytokine tumour necrosis factor-¦Á in human blood and human monocytic cells and indicate whether this action involved the same receptor systems/signals as PGE₂.

Experimental approach

Whole human blood, monocytes isolated from the blood or the human monocytic cell line THP-1 was incubated with LPS and the level of TNF-¦Á produced was measured by ELISA assay. The actions of PGE₂-EA were assessed on the LPS-induced TNF-¦Á release. In addition, in order to ascertain the receptors involved, the levels of cyclic AMP in cells were measured in monocytes and THP-1 cells in response to PGE₂-EA and directly compared to those of PGE₂. The effect of PGE₂-EA on the binding of radiolabelled PGE₂ to cells was also measured. Cells were incubated with radiolabelled arachidonic acid and ethanolamine to estimate the production of PGE₂-EA.

Key results

PGE₂-EA potently suppressed TNF-¦Á production in blood, monocytes and the cell line THP-1 in a concentration-dependent manner. This occurred via cyclic AMP pathways as indicated by agents which interfere with these pathways and also direct ligand binding experiments. It was also shown that the cells were able to endogenously produce PGE₂-EA.

Conclusions and implications

This study reports that PGE₂-EA can downregulate the production of TNF-¦Á by human mononuclear cells in response to an immune stimulus, i.e. LPS-activated TLR4, and that this appears to occur via a cAMP-dependent mechanism that most likely involves binding to the EP₂ receptor.