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

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...

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Main Authors: Jeongmin Song, Matthew J Duncan, Guojie Li, Cheryl Chan, Richard Grady, Ann Stapleton, Soman N Abraham
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-04-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.0030060
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author Jeongmin Song
Matthew J Duncan
Guojie Li
Cheryl Chan
Richard Grady
Ann Stapleton
Soman N Abraham
author_facet Jeongmin Song
Matthew J Duncan
Guojie Li
Cheryl Chan
Richard Grady
Ann Stapleton
Soman N Abraham
author_sort Jeongmin Song
collection DOAJ
description 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.
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spelling doaj.art-3595cf58b28e4ef9acf346d73856d29a2022-12-21T22:36:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-04-0134e6010.1371/journal.ppat.0030060A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.Jeongmin SongMatthew J DuncanGuojie LiCheryl ChanRichard GradyAnn StapletonSoman N AbrahamThe 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.https://doi.org/10.1371/journal.ppat.0030060
spellingShingle Jeongmin Song
Matthew J Duncan
Guojie Li
Cheryl Chan
Richard Grady
Ann Stapleton
Soman N Abraham
A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
PLoS Pathogens
title A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
title_full A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
title_fullStr A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
title_full_unstemmed A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
title_short A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.
title_sort novel tlr4 mediated signaling pathway leading to il 6 responses in human bladder epithelial cells
url https://doi.org/10.1371/journal.ppat.0030060
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