title: DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB.
abstract: 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.
authors: Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Llandaff, Cardiff, Wales CF5 2YB, UK. kmorris@uwic.ac.uk
authors: R H K
authors: RH
authors: Morris
authors: A J
authors: AJ
authors: Tonks
authors: K P
authors: KP
authors: Jones
authors: M K
authors: MK
authors: Ahluwalia
authors: A W
authors: AW
authors: Thomas
authors: A
authors: A
authors: Tonks
authors: S K
authors: SK
authors: Jackson
mesh_terms: 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
chemical_list: 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