Heterogeneous Porphyromonas gingivalis LPS modulates immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in human gingival fibroblasts.
Heterogeneous Porphyromonas gingivalis LPS modulates immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in human gingival fibroblasts.
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DOI：
10.1038/srep29829
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发表时间：
2016-08-19
影响因子：
4.6
通讯作者：
Jin L
中科院分区：
文献类型：
--
作者：
Herath TDK;Darveau RP;Seneviratne CJ;Wang CY;Wang Y;Jin L
牙周病（牙龈）是一种高度流行的感染和炎症，占世界各地成年人口的大多数牙齿脱落。牙龈卟啉单胞菌（Porphyromonas gingivalis）是牙周病的重要致病菌，其脂多糖（PgLPS）是其致病的主要因素。在此，我们破译了人牙龈成纤维细胞（HGF）对四酰化PgLPS 1435/1449和五酰化PgLPS 1690两种特征亚型的总体宿主反应，并参考E. coli LPS的蛋白质组学研究。这项研究揭示了差异表达的新的生物标志物的免疫炎症反应，抗氧化防御和细胞骨架动力学的HGF。PgLPS 1690极大地上调炎性蛋白（例如亲环蛋白、诱导型一氧化氮合酶、膜联蛋白、半乳糖凝集素、组织蛋白酶和热休克蛋白），而抗炎蛋白（例如膜联蛋白A2和膜联蛋白A6）被PgLPS 1435/1449显著上调。有趣的是，抗氧化剂蛋白质，如线粒体含锰超氧化物歧化酶和peroxiredoxin 5只上调PgLPS 1690。这些PgLPS异构体的细胞骨架修复相关蛋白，如肌球蛋白的差异调节。本研究对牙龈卟啉单胞菌脂多糖脂质A部分的生物学特性提供了新的见解，该部分可以关键地调节HGFs中的免疫炎症反应、抗氧化防御和细胞骨架动力学，从而增强我们对牙周发病机制的理解。
Periodontal (gum) disease is a highly prevalent infection and inflammation accounting for the majority of tooth loss in adult population worldwide. Porphyromonas gingivalis is a keystone periodontal pathogen and its lipopolysaccharide (PgLPS) acts as a major virulence attribute to the disease. Herein, we deciphered the overall host response of human gingival fibroblasts (HGFs) to two featured isoforms of tetra-acylated PgLPS1435/1449 and penta-acylated PgLPS1690 with reference to E. coli LPS through quantitative proteomics. This study unraveled differentially expressed novel biomarkers of immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in HGFs. PgLPS1690 greatly upregulated inflammatory proteins (e.g. cyclophilin, inducible nitric oxide synthase, annexins, galectin, cathepsins and heat shock proteins), whereas the anti-inflammatory proteins (e.g. Annexin A2 and Annexin A6) were significantly upregulated by PgLPS1435/1449. Interestingly, the antioxidants proteins such as mitochondrial manganese-containing superoxide dismutase and peroxiredoxin 5 were only upregulated by PgLPS1690. The cytoskeletal rearrangement-related proteins like myosin were differentially regulated by these PgLPS isoforms. The present study gives new insight into the biological properties of P. gingivalis LPS lipid A moiety that could critically modulate immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in HGFs, and thereby enhances our understanding of periodontal pathogenesis.