DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB.
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 PGE(2) (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-kappaB 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-alpha-phosphatidylcholine beta-arachidonoyl-gamma-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.
Morris
R H K
RH
Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Llandaff, Cardiff, Wales CF5 2YB, UK. kmorris@uwic.ac.uk
Tonks
A J
AJ
Jones
K P
KP
Ahluwalia
M K
MK
Thomas
A W
AW
Tonks
A
A
Jackson
S K
SK
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone