Porphyromonas gingivalis Lipopolysaccharide Is Both Agonist and Antagonist for p38 Mitogen-Activated Protein Kinase Activation

Lipopolysaccharide (LPS) is a key inflammatory mediator. It has been proposed to function as an important molecule that alerts the host of potential bacterial infection. Although highly conserved, LPS contains important structural differences among different bacterial species that can significantly alter host responses. For example, LPS obtained from Porphyromonas gingivalis, an etiologic agent for periodontitis, evokes a highly unusual host cell response. Human monocytes respond to this LPS by the secretion of a variety of different inflammatory mediators, while endothelial cells do not. In addition, P. gingivalis LPS inhibits endothelial cell expression of E-selectin and interleukin 8 (IL-8) induced by other bacteria. In this report the ability of P. gingivalis LPS to activate p38 mitogen-activated protein (MAP) kinase was investigated. It was found that p38 MAP kinase activation occurred in response to P. gingivalis LPS in human monocytes. In contrast, no p38 MAP kinase activation was observed in response to P. gingivalis LPS in human endothelial cells or CHO cells transfected with human Toll-like receptor 4 (TLR-4). In addition, P. gingivalis LPS was an effective inhibitor of Escherichia coli-induced p38 MAP kinase phosphorylation in both endothelial cells and CHO cells transfected with human TLR-4. These data demonstrate that P. gingivalis LPS activates the LPS-associated p38 MAP kinase in monocytes and that it can be an antagonist for E. coli LPS activation of p38 MAP kinase in endothelial and CHO cells. These data also suggest that although LPS is generally considered a bacterial component that alerts the host to infection, LPS from P. gingivalis may selectively modify the host response as a means to facilitate colonization.

脂多糖（Lipopolysaccharide, LPS）是一类关键的炎症介质。学界已提出其可作为向宿主预警潜在细菌感染的重要分子。尽管LPS具有高度保守性，但不同细菌物种来源的LPS存在重要结构差异，这些差异可显著改变宿主的免疫应答。例如，作为牙周炎致病菌的牙龈卟啉单胞菌（Porphyromonas gingivalis）所提取的LPS，可引发极为特殊的宿主细胞应答：人类单核细胞会通过分泌多种不同的炎症介质对该LPS产生响应，而内皮细胞则无此反应。此外，牙龈卟啉单胞菌LPS可抑制其他细菌诱导的内皮细胞E-选择素（E-selectin）与白细胞介素8（IL-8）的表达。本研究探究了牙龈卟啉单胞菌LPS激活p38丝裂原活化蛋白（mitogen-activated protein, MAP）激酶的能力。研究发现，人类单核细胞在接触牙龈卟啉单胞菌LPS后，会发生p38 MAP激酶的激活；与之相反，在人类内皮细胞或转染了人Toll样受体4（Toll-like receptor 4, TLR-4）的中国仓鼠卵巢（CHO）细胞中，并未观察到牙龈卟啉单胞菌LPS诱导的p38 MAP激酶激活。此外，在人类内皮细胞与转染了人TLR-4的CHO细胞中，牙龈卟啉单胞菌LPS可有效抑制大肠杆菌（Escherichia coli）诱导的p38 MAP激酶磷酸化。上述实验数据表明，牙龈卟啉单胞菌来源的LPS可在单核细胞中激活与LPS相关的p38 MAP激酶，同时可作为拮抗剂，抑制大肠杆菌LPS在内皮细胞与CHO细胞中对p38 MAP激酶的激活作用。本研究数据同时提示，尽管通常认为LPS是向宿主预警细菌感染的细菌组分，但牙龈卟啉单胞菌来源的LPS或可通过选择性调控宿主应答，以促进自身的定植。