Polydatin up-regulates clara cell secretory protein to suppress phospholipase A2 of lung induced by LPS in vivo and in vitro

Shu Shiyu,Zhang Tianbao,Ye Mao,Chen Jie,Bo Lin,Li Tingyu,Ling Zhiyu,Wang Lijia

doi:10.1186/1471-2121-12-31

Abstract

BackgroundLung injury induced by lipopolysaccharide (LPS) remains one of the leading causes of morbidity and mortality in children. The damage to membrane phospholipids leads to the collapse of the bronchial alveolar epithelial barrier during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Phospholipase A2 (PLA2), a key enzyme in the hydrolysis of membrane phospholipids, plays an important traumatic role in pulmonary inflammation, and Clara cell secretory protein (CCSP) is an endogenous inhibitor of PLA2. Our previous study showed that polydatin (PD), a monocrystalline extracted from a traditional Chinese medicinal herb (Polygonum cuspidatum Sieb, et Zucc), reduced PLA2 activity and sPLA2-IIA mRNA expression and mitigated LPS-induced lung injury. However, the potential mechanism for these effects has not been well defined. We have continued to investigate the effect of PD on LPS-induced expression of CCSP mRNA and protein in vivo and in vitro.ResultsOur results suggested that the CCSP mRNA level was consistent with its protein expression. CCSP expression was decreased in lung after LPS challenge. In contrast, PD markedly increased CCSP expression in a concentration-dependent manner. In particular, CCSP expression in PD-pretreated rat lung was higher than in rats receiving only PD treatment.ConclusionThese results indicated that up-regulation of CCSP expression causing inhibition of PLA2 activation may be one of the crucial protective mechanisms of PD in LPS-induced lung injury.

Highlights

Lung injury induced by lipopolysaccharide (LPS) remains one of the leading causes of morbidity and mortality in children
Polydatin down-regulates sPLA2 and classes: high-molecular-weight intracellular PLA2 (cPLA2) mRNA expression in rat lung Because ciliated bronchiolar (Clara) cell secretory protein (CCSP) was the potential inhibitor of Phospholipase A2 (PLA2), we investigated the effects of PD on PLA2 along with CCSP
The results indicated that LPS inhibited the protein expression of CCSP and that PD treatment and PD pretreatment increased the level of CCSP markedly (Figure 7A and 7B)

Summary

Introduction

Lung injury induced by lipopolysaccharide (LPS) remains one of the leading causes of morbidity and mortality in children. The damage to membrane phospholipids leads to the collapse of the bronchial alveolar epithelial barrier during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Our previous study showed that polydatin (PD), a monocrystalline extracted from a traditional Chinese medicinal herb (Polygonum cuspidatum Sieb, et Zucc), reduced PLA2 activity and sPLA2-IIA mRNA expression and mitigated LPS-induced lung injury. We have continued to investigate the effect of PD on LPS-induced expression of CCSP mRNA and protein in vivo and in vitro. Acute lung injury (ALI), or its severe form, acute respiratory distress syndrome (ARDS), induced by sepsis is still a major cause of morbidity and mortality in children [1]. Improved treatments and prevention strategies are needed to minimize the mortality associated with ALI

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