Putnins Edward E, Sanaie Ali-Reza, Wu Qiang, Firth James D
Department of Oral Biological and Medical Sciences University of British Columbia, Vancouver, Canada.
Infect Immun. 2002 Dec;70(12):6541-8. doi: 10.1128/IAI.70.12.6541-6548.2002.
Periodontal disease is a chronic inflammatory condition that is associated with increased concentrations of gram-negative pathogenic bacteria and epithelial cell proliferation. Regulation of this proliferation is poorly understood but is most likely controlled by locally expressed growth factors. Keratinocyte growth factor 1, an epithelium-specific growth factor, is expressed by gingival fibroblasts, and its expression is regulated in a concentration-dependent manner by lipopolysaccharide. In this study, induction of keratinocyte growth factor 1 protein expression was dependent on gingival fibroblast expression of membrane CD14 (mCD14) and Toll-like receptors 2 and 4. Lipopolysaccharides from Escherichia coli and Porphyromonas gingivalis induced membrane expression of CD14 at 1, 3, and 24 h. Specifically, lipopolysaccharide induced low mCD14 expression gingival fibroblasts to express mCD14 at a level consistent with that of high mCD14 expression cells. Functional studies with specific blocking antibodies for CD14 and Toll-like receptors 2 and 4 implicated all of these molecules in signal transduction. The rapid decrease in cell membrane expression of Toll-like receptors 2 and 4 after treatment with lipopolysaccharide was consistent with receptor internalization, and blocking of either of these receptors completely inhibited keratinocyte growth factor 1 protein expression. The transcription factors AP-1 and NF-kappaB were involved in lipopolysaccharide induction of keratinocyte growth factor 1 mRNA and protein expression. These results suggest that lipopolysaccharide may induce proliferation of periodontal epithelial cells by upregulating keratinocyte growth factor 1 expression via the CD14 and Toll-like receptor signaling pathway.
牙周病是一种慢性炎症性疾病，与革兰氏阴性病原菌浓度增加和上皮细胞增殖有关。这种增殖的调控机制尚不清楚，但很可能由局部表达的生长因子控制。角质形成细胞生长因子1是一种上皮特异性生长因子，由牙龈成纤维细胞表达，其表达受脂多糖浓度依赖性调节。在本研究中，角质形成细胞生长因子1蛋白表达的诱导依赖于牙龈成纤维细胞膜CD14（mCD14）以及Toll样受体2和4的表达。大肠杆菌和牙龈卟啉单胞菌的脂多糖在1、3和24小时诱导CD14的膜表达。具体而言，脂多糖诱导低mCD14表达的牙龈成纤维细胞表达mCD14，其水平与高mCD14表达细胞一致。使用针对CD14以及Toll样受体2和4的特异性阻断抗体进行的功能研究表明，所有这些分子都参与信号转导。脂多糖处理后Toll样受体2和4的细胞膜表达迅速下降，这与受体内化一致，阻断这些受体中的任何一个都完全抑制角质形成细胞生长因子1蛋白表达。转录因子AP-1和NF-κB参与脂多糖对角质形成细胞生长因子1 mRNA和蛋白表达的诱导。这些结果表明，脂多糖可能通过CD14和Toll样受体信号通路上调角质形成细胞生长因子1的表达，从而诱导牙周上皮细胞增殖。
