TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14

• Epithelial cells lining the urinary bladder mucosa are engaged in numerous functions that act in concert to prevent exposure of the sensitive upper urinary tract to bacteria. This protective effect was recently suggested to be achieved mainly by compartmentalized, organ-specific expression of the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR) 4 within epithelial cells of the urogenital tract. Here, we show that bladder epithelial cells recognize similarly low amounts of LPS as macrophages. LPS responsiveness measured as secretion of the chemoattractant interleukin 8 demonstrates a dependency on TLR4 in epithelial cells, which is similar to the situation in macrophages. The TLR4-mediated LPS response in bladder epithelial cells also uses the co-receptor CD14 for efficient LPS signalling. However, bladder epithelial cells do not express endogenous CD14 and are therefore dependent on the soluble form of CD14 that is present in body fluids. Furthermore, we demonstrate that epithelial chemokine production is augmented by type 1-mediated attachment of uropathogenic Escherichia coli in the absence, but not in the presence, of CD14. Collectively, our findings strengthen the role for bladder epithelial cells as important players in the innate immune system within the urinary tract.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Antigens

CD14/ metabolism

Culture Media

Serum-Free

Drosophila Proteins

Epithelial Cells/metabolism

Escherichia coli/pathogenicity

Humans

Interleukin-1/immunology/pharmacology

Interleukin-8/secretion

Lipopolysaccharides/immunology/ metabolism/pharmacology

Membrane Glycoproteins/ metabolism

Receptors

Cell Surface/ metabolism

Recombinant Proteins/metabolism

Signal Transduction

Toll-Like Receptor 4

Toll-Like Receptors

Tumor Cells

Cultured

Urinary Bladder/cytology/metabolism

Urothelium/cytology/ metabolism

Publication and Content Type

ref (subject category)

art (subject category)