CCL20 Is an Inducible Product of Human Airway Epithelia with Innate Immune Properties

Timothy D. Starner, Carrie K. Barker, Hong Peng Jia, Yubin Kang, Paul B. McCray

Research output: Contribution to journalArticlepeer-review

Abstract

Chemokine ligand 20 (CCL20) and human β-defensins (HBDs) share structural and functional properties, including antiparallel β-pleated sheet core structures, charge distribution, and signaling to adaptive immune cells via the highly selective CCR6 receptor. Because of their similarities, we hypothesized that in addition to its known adaptive immune signaling functions, CCL20 has antimicrobial properties and participates in pulmonary innate immunity. We found that primary cultures of human airway epithelial and cultured fetal lung explants expressed CCL20 mRNA. Expression of CCL20 transcripts were significantly induced by interleukin (IL)-1β and tumor necrosis factor-α, and inhibited by dexamethasone. Primary cultures of airway epithelia secreted CCL20 both apically and basolaterally, and CCL20 abundance was increased over 30-fold with IL-1β stimulation, achieving an estimated concentration of 167 ng/ml in airway surface liquid. CCL20 abundance in bronchoalveolar lavage fluid from patients with cystic fibrosis was nearly 90-fold higher compared with bronchoalveolar lavage fluid from healthy volunteers. Interestingly, CCL20 exhibited salt-sensitive antimicrobial activity, mainly against Gram-negative bacteria in low μg/ml concentrations. Additionally, apical washings from IL-1β-stimulated primary cultures of human airway epithelia had significantly more antimicrobial activity than unstimulated controls. CCL20 rapidly permeabilized bacterial membranes with a time course intermediate to HBD-2 and HBD-3. Thus, CCL20 is a bi-functional peptide with both innate and adaptive immune properties that is regulated by inflammatory mediators, expressed by airway epithelia, and increased in cystic fibrosis airway secretions.

Original languageEnglish (US)
Pages (from-to)627-633
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume29
Issue number5
DOIs
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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