DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB

https://doi.org/10.1016/j.bbrc.2008.03.052Get rights and content

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 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.

Section snippets

Materials and methods

Preparation of lipid media.l-α-Phosphatidylcholine dipalmitoyl (DPPC), l-α-phosphatidylcholine β-arachidonoyl-γ-palmitoyl (PAPC), were purchased from Sigma Chemical Co. (Dorset, UK) and prepared as previously described [9].

Human monocyte cell culture. The human monocytic cell-line MonoMac-6 (MM6) was cultured as previously described [9]. The viability of MM6 cells exposed to lipid was greater than 90% throughout. Human peripheral blood monocytes were isolated from adult non-smoking volunteers

The effect of DPPC on PGE2 synthesis and secretion in human monocytes

Previously we have shown that surfactant phospholipids modulate TNF-α production in human monocytes and at the same time increased the production of PGE2[8]. In order to determine whether the disaturated form of PC (DPPC; the major constituent of surfactant) also had a similar effect, we incubated DPPC (250 μg/ml) with human monocytes. When the human monocytic cell line MM6 was incubated with DPPC for up to 8 h, there was a significant production of PGE2 (2.5-fold) when compared to untreated

Discussion

Pulmonary surfactant lipids demonstrate immuno-regulatory roles in addition to their effects on alveolar surface tension [1], [2]. In particular, the major surfactant lipid, DPPC, has shown anti-inflammatory activity in a number of cell types [4], [8], [9], [10], [11]. The inflammatory response in the lungs could initiate or potentiate the development of many inflammatory lung diseases, including acute respiratory distress syndrome, cystic fibrosis, idiopathic pulmonary fibrosis, and chronic

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