Surfactant protein D inhibits lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human renal tubular epithelial cells: implication for tubulointerstitial fibrosis
Surfactant protein D inhibits lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human renal tubular epithelial cells: implication for tubulointerstitial fibrosis
复制标题
表面活性剂蛋白 D 抑制人肾小管上皮细胞中脂多糖诱导的单核细胞趋化蛋白-1 表达：对肾小管间质纤维化的影响
DOI：
10.1111/j.1365-2249.2011.04521.x
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发表时间：
2012-03-01
影响因子：
4.6
通讯作者：
Ding, G.
中科院分区：
文献类型：
--
作者：
Hu, F.;Liang, W.;Ding, G.
表面活性蛋白D(SP-D)是C型凝集素(集合素)蛋白家族的一员，在机体对多种微生物的天然防御和肺部炎症反应的调节中发挥着重要作用。然而，人们对其在肾脏中的表达和生物学功能知之甚少。本工作研究了SP-D在人肾脏和培养的人肾小管上皮细胞(HK-2)中的表达，并探讨了SP-D对内毒素(LPS)刺激后促炎症细胞因子产生的影响。采用免疫组织化学、Western印迹分析、逆转录聚合酶链式反应(RT-PCR)和实时定量聚合酶链式反应(Real-time PCR)等方法，观察SP-D在人肾和体外培养的HK-2细胞中的表达。为探讨SP-D在肾感染肾小管间质纤维化发病机制中的作用，我们检测了脂多糖对HK-2细胞产生单核细胞趋化蛋白-1(MCP-1)的影响。结果表明，加入内毒素(0.1mU/ml)8h后，HK-2细胞条件培养液中单核细胞趋化蛋白-1(MCP-1)水平显著升高，且抑制了细胞SP-D的表达。此外，SP-D的过表达显著降低了脂多糖诱导的MCP-1的表达。这些结果提示，肾脏中的SP-D在肾小管上皮细胞中发挥抗炎因子的作用，并可能调节肾小管间质纤维化。
Surfactant protein D (SP-D), a member of the C-type lectin (collectin) protein family, plays a critical role in innate host defence against various microbial pathogens and in the modulation of inflammatory responses in the lung. However, little is known about its expression and biological function in the kidney. In this work, we studied SP-D expression in human kidney and cultured human renal proximal tubular epithelial cells (HK-2), and examined the effect of SP-D on proinflammatory cytokine production after lipopolysaccharide (LPS) stimulus. We observed the expression of both SP-D mRNA and protein in human kidney and in-vitro HK-2 cells by immunohistochemistry, Western blot analysis, reverse transcriptionpolymerase chain reaction (RTPCR) and real-time PCR. To explore the potential role of SP-D in the pathogenesis of tubulointerstitial fibrosis in kidney infection, we examined the production of monocyte chemoattractant protein-1 (MCP-1) in HK-2 cells after LPS treatment. Results showed that the level of MCP-1 in the conditioned medium increased significantly when HK-2 cells were cultured with LPS (>0.1 mu g/ml) for 8 h. Of interest, LPS treatment inhibited SP-D expression in HK-2 cells. Furthermore, over-expression of SP-D reduced significantly the LPS-induced expression of MCP-1 in transfected cells. These findings suggest that SP-D in the kidney functions as an anti-inflammatory factor in renal tubular epithelial cells and may modulate tubulointerstitial fibrosis in kidney.