ArticleThe Journal of clinical investigation2012
Cytokeratins mediate epithelial innate defense through their antimicrobial properties.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Keratinocytes as active regulators of cutaneous and mucosal immunity: a systematic review across inflammatory epithelial disorders.Frontiers in immunology · 2025Pooled it
- Keratin filaments and soluble vimentin interact with isoform specificity to organize cell signaling.Genes & development · 2026Article
- Prior contact lens wear reduces susceptibility of the superficially-injured cornea to bacterial adhesion.PloS one · 2026Article
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- TRPV1 Defends the Healthy Murine Cornea Against Staphylococcus aureus Adhesion Independently of Sensory Nerve Firing.Investigative ophthalmology & visual science · 2025Article
- ThemBio · 2025Article
- Modulation of cytokeratin and cytokine/chemokine expression following influenza virus infection of differentiated human tonsillar epithelial cells.Journal of virology · 2025Article
- Contact Lens Wear Alters Transcriptional Responses to Pseudomonas aeruginosa in Both the Corneal Epithelium and the Bacteria.Investigative ophthalmology & visual science · 2025Article
- Contact Lens Wear Alters Transcriptional Responses tobioRxiv : the preprint server for biology · 2024Article
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Darier's disease exhibits a unique cutaneous microbial dysbiosis associated with inflammation and body malodour.Microbiome · 2023Article
- Simultaneous control of infection and inflammation with keratin-derived antibacterial peptides targeting TLRs and co-receptors.Science translational medicine · 2023Article
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides.Biomedicines · 2021Review
- Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility.The ocular surface · 2021Article
- Nerve-associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Foundational concepts in the biology of bacterial keratitis.Experimental eye research · 2021Review
- Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer's Disease Using Network Analysis of Proteomics Datasets.Frontiers in genetics · 2021Article
- Antimicrobial Peptides and Proteins: From Nature's Reservoir to the Laboratory and Beyond.Frontiers in chemistry · 2021Review
- Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy inInternational journal of molecular sciences · 2020Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial cells express antimicrobial proteins in response to invading pathogens, although little is known regarding epithelial defense mechanisms during healthy conditions. Here we report that epithelial cytokeratins have innate defense properties because they constitutively produce cytoprotective antimicrobial peptides. Glycine-rich C-terminal fragments derived from human cytokeratin 6A were identified in bactericidal lysate fractions of human corneal epithelial cells. Structural analysis revealed that these keratin-derived antimicrobial peptides (KDAMPs) exhibited coil structures with low α-helical content. Synthetic analogs of these KDAMPS showed rapid bactericidal activity against multiple pathogens and protected epithelial cells against bacterial virulence mechanisms, while a scrambled peptide showed no bactericidal activity. However, the bactericidal activity of a specific KDAMP was somewhat reduced by glycine-alanine substitutions. KDAMP activity involved bacterial binding and permeabilization, but the activity was unaffected by peptide charge or physiological salt concentration. Knockdown of cytokeratin 6A markedly reduced the bactericidal activity of epithelial cell lysates in vitro and increased the susceptibility of murine corneas to bacterial adherence in vivo. These data suggest that epithelial cytokeratins function as endogenous antimicrobial peptides in the host defense against infection and that keratin-derived antimicrobials may serve as effective therapeutic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.