Published ahead of print on May 14, 2003, doi:10.1165/rcmb.2002-0272OC
Am. J. Respir. Cell Mol. Biol., Volume 29, Number 5, November 2003, 627-633
A more recent version of this article appeared on November 1, 2003
Submitted on November 26, 2002
Revised on May 13, 2003
CCL20 is an inducible product of human airway epithelia with innate immune properties
Timothy D Starner1, Carrie K Barker1, Hong P Jia1, Yubin Kang1, and Paul B McCray1*
1 Pediatrics, University of Iowa, Iowa City, Iowa, USA
* To whom correspondence should be addressed. E-mail: paul-mccray{at}uiowa.edu.
Chemokine ligand 20 (CCL20) and human beta-defensins (HBDs) share structural and functional properties, including anti-parallel  -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 IL-1 and TNF- , 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-1 stimulation, achieving an estimated concentration of 167 ng/ml in airway surface liquid. CCL20 abundance in bronchoalveolar lavage fluid (BALF) from patients with cystic fibrosis (CF) was nearly 90-fold higher compared to BALF 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-1 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 CF airway secretions.
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