Morris R H K, Tonks A J, Jones K P, Ahluwalia M K, Thomas A W, Tonks A, Jackson S K
Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Llandaff, Cardiff, Wales CF5 2YB, UK.
Biochem Biophys Res Commun. 2008 May 23;370(1):174-8. doi: 10.1016/j.bbrc.2008.03.052. Epub 2008 Mar 18.
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.
肺表面活性物质中的主要磷脂二棕榈酰磷脂酰胆碱（DPPC）已被证明可调节炎症反应。本研究利用人类单核细胞表明，与未处理的单核细胞对照相比，DPPC可使PGE(2)的产生显著增加2.5倍（P<0.05）。从机制上讲，这种效应与COX-2表达的增加同时出现，而在存在COX-2抑制剂的情况下这种增加被消除。COX-2表达的调节独立于NF-κB活性。此外，DPPC增加了环磷酸腺苷反应元件结合蛋白（CREB，一种在调节COX-2表达中起重要作用的核转录因子）的磷酸化。此外，我们还表明，改变磷脂酰胆碱的脂肪酸基团（例如使用l-α-磷脂酰胆碱β-花生四烯酰-γ-棕榈酰（PAPC））对COX-2表达的调节和CREB激活有深远影响。本研究为DPPC的抗炎活性提供了新证据，且该活性至少部分是通过CREB对COX-2的激活介导的。
