Journal article
CCL20 is an inducible product of human airway epithelia with innate immune properties
American journal of respiratory cell and molecular biology, Vol.29(5), pp.627-633
11/2003
DOI: 10.1165/rcmb.2002-0272OC
PMID: 12748059
Abstract
Chemokine ligand 20 (CCL20) and human beta-defensins (HBDs) share structural and functional properties, including antiparallel beta-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)-1beta and tumor necrosis factor-alpha, 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-1beta 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 mug/ml concentrations. Additionally, apical washings from IL-1beta-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.
Details
- Title: Subtitle
- CCL20 is an inducible product of human airway epithelia with innate immune properties
- Creators
- Timothy D Starner - Department of Pediatrics, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USACarrie K BarkerHong Peng JiaYubin KangPaul B McCray Jr
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.29(5), pp.627-633
- DOI
- 10.1165/rcmb.2002-0272OC
- PMID
- 12748059
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Grant note
- HL67992-01 / NHLBI NIH HHS HL07638 / NHLBI NIH HHS HL61234 / NHLBI NIH HHS P30 DK54759 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/2003
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093499602771
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