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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Song, J; Duncan, MJ; Li, G; Chan, C; Grady, R; Stapleton, A; Abraham, SN

Published Date

  • April 1, 2007

Published In

Volume / Issue

  • 3 / 4

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.0030060

Citation Source

  • Scopus