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The chemokine CXCL14/BRAK has antimicrobial activity [Abstract]

Märki, C., Liebi, M., Ackermann, U., Mühlemann, K., Frederick, M., Moser, Bernhard and Wolf, M. 2008. The chemokine CXCL14/BRAK has antimicrobial activity [Abstract]. Swiss Medical Weekly (S163) , 44S.

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Several chemokines possess potent killing activity against bacteria and fungi, similar to antimicrobial peptides such as defensins and cathelicidins. The antimicrobial activity of chemokines is explained by their high cationicity and the topological formation of large, positive electrostatic patches on the surface of the molecule, features they share with defensins and which allow electrostatic interaction with the anionic moieties on the surface of bacteria thereby disrupting the integrity of their membrane. The chemokine CXCL14/BRAK is constitutively expressed in healthy skin, notably in keratinocytes and dermal fibroblasts, but also in other epithelial tissues. Its function, however, is poorly characterized and its receptor still unknown. Due to its prominent expression at physical barriers, we hypothesized CXCL14/BRAK to be a candidate among the chemokines to act as an antimicrobial peptide. We examined gram-negative and gram-positive bacteria and the fungus Candida albicans, microorganisms which preferentially colonize skin and mucosa, for being susceptible to CXCL14/BRAK. The antimicrobial activity of CXCL14 was evaluated by the radial diffusion assay and was compared to that of the chemokines CCL20, CCL27, CXCL8 and to human beta-defensin-2, a prototype antimicrobial peptide in skin. We found that CXCL14/BRAK exhibits strong activity against Escherichia coli, Staphylococcus aureus, coagulase-negative Staphylococci, Propionibacteria and Candida albicans. CXCL14/BRAK was more potent against these organisms than the other chemokines and also more potent than human beta-defensin-2. A relevant antimicrobial effect of CXCL14/BRAK against Escherichia coli was observed at a concentration as low as 50nM. Moreover, culture supernatants of CXCL14/BRAK-transfected cell lines exhibit significantly stronger antimicrobial activity than supernatants of respective parental cell lines. The antimicrobial activity is highly specific for CXCL14/BRAK and is reduced to a large extent by adding an anti-CXCL14 antibody. Altogether, we describe an important new function of CXCL14/BRAK by showing that this chemokine exhibits strong antimicrobial activity and therefore may be involved as a local host defence molecule protecting healthy skin and possibly other epithelia from infection by various microbes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Additional Information: Abstract for the Annual joint meeting of the Swiss Societies for Pneumology, Paediatric Pneumology, Allergology and Immunology, Thoracic Surgery
Publisher: Swiss Medical Publishers Ltd./EMH Medical Publications
ISSN: 1424-7860
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Last Modified: 04 Jun 2017 03:08

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