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A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.


ABSTRACT: 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.

SUBMITTER: Song J 

PROVIDER: S-EPMC1857715 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.

Song Jeongmin J   Duncan Matthew J MJ   Li Guojie G   Chan Cheryl C   Grady Richard R   Stapleton Ann A   Abraham Soman N SN  

PLoS pathogens 20070401 4


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,  ...[more]

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