Candida albicans induces cyclo-oxygenase 2 expression and prostaglandin E2 production in synovial fibroblasts through an extracellular-regulated kinase 1/2 dependent pathway
Candida albicans induces cyclo-oxygenase 2 expression and prostaglandin E2 production in synovial fibroblasts through an extracellular-regulated kinase 1/2 dependent pathway
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DOI：
10.1186/ar2661
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发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Salter, Donald M.
中科院分区：
文献类型：
--
作者：
Lee, Herng-Sheng;Lee, Chung-Shinn;Salter, Donald M.
滑膜细胞是细菌诱导关节炎炎症介质的潜在来源，但它们在白色念珠菌诱导的脓毒性关节炎炎症反应中的作用在很大程度上是未知的。方法原代培养大鼠滑膜成纤维细胞感染白色念珠菌（ATCC90028）。免疫细胞化学、western blotting和RT-PCR检测环加氧酶2的诱导作用。在U0126缺失或存在的情况下，通过western blotting评估感染后细胞外调节激酶（ERK1/2）的磷酸化水平，同时通过ELISA检测前列腺素E2的产生。核因子κ B （NF κ B）易位通过电泳迁移转移法进行评估。结果白色念珠菌感染滑膜成纤维细胞可引起环加氧酶2的表达和前列腺素E2的产生。环加氧酶2的表达和前列腺素E2的产生依赖于细胞外调节的激酶1/2磷酸化，与NF κ B的激活有关，并且在层粘连蛋白（dectin-1活性抑制剂）存在时显著升高。白色念珠菌菌丝聚集体附近的滑膜成纤维细胞似乎是环加氧酶2和磷酸化的细胞外调节激酶1/2水平升高的主要原因。结论白色念珠菌感染滑膜成纤维细胞导致环加氧酶2和前列腺素E2的上调，其机制可能涉及细胞外调节激酶1/2的激活，并与NF κ B的激活有关。
Introduction Synovial cells are potential sources of inflammatory mediators in bacterial-induced arthritis but their involvement in the inflammatory response to Candida albicans-induced septic arthritis is largely unknown.Methods Primary cultures of rat synovial fibroblasts were infected with C. albicans (ATCC90028). Immunocytochemistry, western blotting, and RT-PCR were performed to assess cyclooxygenase 2 induction. Phosphorylation of extracellular-regulated kinase (ERK1/2) following infection in the absence or presence of U0126 was assessed by western blotting whilst prostaglandin E2 production was measured by ELISA. Nuclear factor kappa B (NF kappa B) translocation was evaluated by an electrophoretic mobility shift assay.Results Infection of synovial fibroblasts with C. albicans resulted in cyclo-oxygenase 2 expression and prostaglandin E2 production. Cyclo-oxygenase 2 expression and prostaglandin E2 production was dependent upon extracellular-regulated kinase 1/2 phosphorylation, associated with activation of NF kappa B and significantly elevated in the presence of laminarin, an inhibitor of dectin-1 activity. Synovial fibroblasts adjacent to C. albicans hyphae aggregates appeared to be the major contributors to the increased levels of cyclo-oxygenase 2 and phosphorylated extracellular-regulated kinase 1/2.Conclusions C. albicans infection of synovial fibroblasts in vitro results in upregulation of cyclo-oxygenase 2 and prostaglandin E2 by mechanisms that may involve activation of extracellular-regulated kinase 1/2 and are associated with NF kappa B activation.