DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB
Morris, R., Tonks, A. J., Jones, K., Ahluwalia, M., Thomas, A., Tonks, A. and Jackson, S. K. (2008) DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB. Biochemical and Biophysical Research Communications, 370 (1). pp. 174-178. ISSN 0006-291X Available from: http://eprints.uwe.ac.uk/7136
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Publisher's URL: http://dx.doi.org/10.1016/j.bbrc.2008.03.052
The major phospholipid in pulmonary surfactant dipalmitoyl phosphatidylcholine (DPPC) has been shown to modulate inflammatory responses. Using human monocytes, this study demonstrates that DPPC significantly increased PGE2 (P < 0.05) production by 2.5-fold when compared to untreated monocyte controls. Mechanistically, this effect was concomitant with an increase in COX-2 expression which was abrogated in the presence of a COX-2 inhibitor. The regulation of COX-2 expression was independent of NF-κB activity. Further, DPPC increased the phosphorylation of the cyclic AMP response element binding protein (CREB; an important nuclear transcription factor important in regulating COX-2 expression). In addition, we also show that changing the fatty acid groups of PC (e.g. using l-α-phosphatidylcholine β-arachidonoyl-γ-palmitoyl (PAPC)) has a profound effect on the regulation of COX-2 expression and CREB activation. This study provides new evidence for the anti-inflammatory activity of DPPC and that this activity is at least in part mediated via CREB activation of COX-2.