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 12n/1200 wella 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 turbosound ts-18sw700/8a 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.