The antimicrobial peptide cathelicidin enhances activation of lung epithelial cells by LPS. Academic Article uri icon

Overview

MeSH

  • Biological Transport
  • Cell Line
  • Cells, Cultured
  • Endocytosis
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Microscopy, Confocal
  • Receptor, Epidermal Growth Factor
  • Signal Transduction

MeSH Major

  • Cathelicidins
  • Epithelial Cells
  • Lipopolysaccharides
  • Lung

abstract

  • Epithelial cells (ECs) are usually hyporesponsive to various microbial products. Detection of lipopolysaccharide (LPS), the major component of gram-negative bacteria, is impeded, at least in part, by intracellular sequestration of its receptor, Toll-like receptor-4 (TLR4). In this study, using human bronchial ECs (hBECs) as a model of mucosal epithelium, we tested the hypothesis that the human LPS-binding, membrane-active cationic host defense peptide cathelicidin LL-37 augments epithelial response to LPS by facilitating its delivery to TLR4-containing intracellular compartments. We found that LL-37 significantly increases uptake of LPS by ECs with subsequent targeting to cholera toxin subunit B-labeled structures and lysosomes. This uptake is peptide specific, dose and time dependent, and involves the endocytotic machinery, functional lipid rafts, and epidermal growth factor receptor signaling. Cathelicidin-dependent LPS internalization resulted in significant increased release of the inflammatory cytokines IL-6 and IL-8. This indicates that, in ECs, this peptide may replace LPS-binding protein functions. In polarized ECs, the effect of LL-37 was restricted to the basolateral compartment of the epithelial membrane, suggesting that LL-37-mediated activation of ECs by LPS may be relevant to disease conditions associated with damage to the epithelial barrier. In summary, our study identified a novel role of LL-37 in host-microbe interactions as a host factor that licenses mucosal ECs to respond to LPS.

publication date

  • December 2010

has subject area

  • Biological Transport
  • Cathelicidins
  • Cell Line
  • Cells, Cultured
  • Endocytosis
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Lipopolysaccharides
  • Lung
  • Microscopy, Confocal
  • Receptor, Epidermal Growth Factor
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1096/fj.09-151332

PubMed ID

  • 20696857

Additional Document Info

start page

  • 4756

end page

  • 4766

volume

  • 24

number

  • 12