Song Jeongmin, Duncan Matthew J, Li Guojie, Chan Cheryl, Grady Richard, Stapleton Ann, Abraham Soman N
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS Pathog. 2007 Apr;3(4):e60. doi: 10.1371/journal.ppat.0030060.
The vigorous cytokine response of immune cells to Gram-negative bacteria is primarily mediated by a recognition molecule, Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide (LPS) and initiates a series of intracellular NF-kappaB-associated signaling events. Recently, bladder epithelial cells (BECs) were reported to express TLR4 and to evoke a vigorous cytokine response upon exposure to LPS. We examined intracellular signaling events in human BECs leading to the production of IL-6, a major urinary cytokine, following activation by Escherichia coli and isolated LPS. We observed that in addition to the classical NF-kappaB-associated pathway, TLR4 triggers a distinct and more rapid signaling response involving, sequentially, Ca(2+), adenylyl cyclase 3-generated cAMP, and a transcriptional factor, cAMP response element-binding protein. This capacity of BECs to mobilize secondary messengers and evoke a more rapid IL-6 response might be critical in their role as first responders to microbial challenge in the urinary tract.
免疫细胞对革兰氏阴性菌产生的强烈细胞因子反应主要由一种识别分子——Toll样受体4（TLR4）介导，该受体识别脂多糖（LPS）并启动一系列与细胞内NF-κB相关的信号事件。最近，有报道称膀胱上皮细胞（BECs）表达TLR4，并在暴露于LPS时引发强烈的细胞因子反应。我们研究了人BECs在被大肠杆菌和分离的LPS激活后，导致主要尿细胞因子IL-6产生的细胞内信号事件。我们观察到，除了经典的与NF-κB相关的途径外，TLR4还触发了一种独特且更快的信号反应，依次涉及Ca(2+)、腺苷酸环化酶3产生的cAMP以及一种转录因子——cAMP反应元件结合蛋白。BECs动员第二信使并引发更快的IL-6反应的这种能力，可能在其作为尿路微生物挑战的第一反应者的角色中至关重要。
