DOI: 10.4049/jimmunol.174.7.4271. Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities

Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities

10.4049/jimmunol.174.7.4271

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract Cathelicidins and other antimicrobial peptides are deployed at epithelial surfaces to defend against infection. These molecules have broad-spectrum killing activity against microbes and can have effects on specific mammalian cell types, potentially stimulating additional immune defense through direct chemotactic activity or induction of cytokine release. In humans, the cathelicidin hCAP18/LL-37 is processed to LL-37 in neutrophils, but on skin it can be further proteolytically processed to shorter forms. The influence of these cathelicidin peptides on keratinocyte function is not known. In the current study, DNA microarray analysis and confirmatory protein analysis showed that LL-37 affects the expression of several chemokines and cytokines by keratinocytes. Analysis of a synthetic peptide library derived from LL-37 showed that antimicrobial activity against bacterial, fungal, and viral skin pathogens resides within specific domains of the parent peptide, but antimicrobial activity does not directly correlate with the ability to stimulate IL-8 production in keratinocytes. IL-8 release was induced by d- and l-amino acid forms of cathelicidin and correlated with membrane permeability, suggesting that highly structure-specific binding to a cell surface receptor is not likely. However, this effect was inhibited by either pertussis toxin or AG1478, an epidermal growth factor receptor tyrosine kinase inhibitor, suggesting that cathelicidin may indirectly stimulate multiple signaling pathways associated with cell surface receptors. Taken together, these observations suggest that proteolytic processing may alter the balance between cathelicidin antimicrobial and host immunostimulatory functions.

Bibliography

Braff, M. H., Hawkins, M. A., Nardo, A. D., Lopez-Garcia, B., Howell, M. D., Wong, C., Lin, K., Streib, J. E., Dorschner, R., Leung, D. Y. M., & Gallo, R. L. (2005). Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities. The Journal of Immunology, 174(7), 4271â4278.

Authors 11

Marissa H Braff (first)
Mi‘i A Hawkins (additional)
Anna Di Nardo (additional)
Belen Lopez-Garcia (additional)
Michael D Howell (additional)
Cathy Wong (additional)
Kenneth Lin (additional)
Joanne E Streib (additional)
Robert Dorschner (additional)
Donald Y M Leung (additional)
Richard L Gallo (additional)

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Dates

Type	When
Created	11 years, 4 months ago (April 22, 2014, 10:39 p.m.)
Deposited	5 months ago (March 30, 2025, 3:01 a.m.)
Indexed	2 days, 4 hours ago (Aug. 29, 2025, 6:43 a.m.)
Issued	20 years, 4 months ago (April 1, 2005)
Published	20 years, 4 months ago (April 1, 2005)
Published Online	20 years, 4 months ago (April 1, 2005)
Published Print	20 years, 4 months ago (April 1, 2005)

Funders 0

None

BibTeX

@article{Braff_2005, title={Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities}, volume={174}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.174.7.4271}, DOI={10.4049/jimmunol.174.7.4271}, number={7}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Braff, Marissa H and Hawkins, Mi‘i A and Nardo, Anna Di and Lopez-Garcia, Belen and Howell, Michael D and Wong, Cathy and Lin, Kenneth and Streib, Joanne E and Dorschner, Robert and Leung, Donald Y M and Gallo, Richard L}, year={2005}, month=apr, pages={4271–4278} }

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