ArticleThe Journal of investigative dermatology2012
Doxycycline indirectly inhibits proteolytic activation of tryptic kallikrein-related peptidases and activation of cathelicidin.
Article in The Journal of investigative dermatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Efficacy of Treatments in Reducing Inflammatory Lesion Count in Rosacea: A Systematic Review.Journal of cutaneous medicine and surgeryPooled it
- Ferulic Acid in the Treatment of Papulopustular Rosacea: A Randomized Controlled Study.Journal of cosmetic dermatology · 2025Trial
- Target site pharmacokinetics of doxycycline for rosacea in healthy volunteers is independent of the food effect.British journal of clinical pharmacology · 2018Trial
- Reduction in serine protease activity correlates with improved rosacea severity in a small, randomized pilot study of a topical serine protease inhibitor.The Journal of investigative dermatology · 2014Trial
- Repurposing of doxycycline as a novel therapeutic avenue for management of parkinson's disease.Inflammopharmacology · 2026Review
- Rosacea scleritis and sclero-uveitis; under recognised and over treated.Journal of ophthalmic inflammation and infection · 2026Review
- Virtual screening identifies specnuezhenide as a potential therapeutic agent for rosacea via KLK5/TLR4/NF-κB pathway inhibition and metabolic modulation.Frontiers in immunology · 2026Article
- Lithospermic acid, a novel KLK5 inhibitor, ameliorates rosacea by suppressing the TLR4/NF-κB signaling pathway and rectifying phenylalanine metabolism.Frontiers in immunology · 2026Article
- Inflammatory memory as a potential driver of rosacea pathogenesis: integrating mechanisms of chronic relapse and perspectives on disease modification.Frontiers in immunology · 2026Review
- Therapeutic effect of an MRGPRX2/MRGPRB2 antagonist on LL-37-induced rosacea-like inflammation in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Influence of sodium Bituminosulfonate and Doxycycline on signal molecules relevant for rosacea symptoms.Scientific reports · 2025Article
- Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Mechanisms and Recent Advances of Small-Molecule Therapeutics in Rosacea Treatment.Clinical, cosmetic and investigational dermatology · 2025Review
- Impaired Angiogenesis and Th1/Th17 Polarization: A Possible Explanation for the Decreased Incidence of Rosacea in the Aged.Immunity, inflammation and disease · 2024Article
- Microencapsulated Benzoyl Peroxide for Rosacea in Context: A Review of the Current Treatment Landscape.Drugs · 2024Review
- Potential Role of Tranexamic Acid in Rosacea Treatment: conquering Flushing Beyond Melasma.Clinical, cosmetic and investigational dermatology · 2024Review
- Signaling pathways and targeted therapy for rosacea.Frontiers in immunology · 2024Review
- Therapeutic strategies focusing on immune dysregulation and neuroinflammation in rosacea.Frontiers in immunology · 2024Review
- Extracellular epimorphin impairs expression and processing of profilaggrin in HaCaT keratinocytes.Cytotechnology · 2023Article
- Role of MrgprB2 in Rosacea-Like Inflammation in Mice: Modulation by β-Arrestin 2.The Journal of investigative dermatology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The increased abundance and activity of cathelicidin and kallikrein 5 (KLK5), a predominant trypsin-like serine protease (TLSP) in the stratum corneum, have been implicated in the pathogenesis of rosacea, a disorder treated by the use of low-dose doxycycline. Here we hypothesized that doxycycline can inhibit activation of tryptic KLKs through an indirect mechanism by inhibition of matrix metalloproteinases (MMPs) in keratinocytes. The capacity of doxycycline to directly inhibit enzyme activity was measured in surface collections of human facial skin and extracts of cultured keratinocytes by fluorescence polarization assay against fluorogenic substrates specific for MMPs or TLSPs. Doxycycline did inhibit MMP activity but did not directly inhibit serine protease activity against a fluorogenic substrate specific for TLSPs. However, when doxycycline or other MMP inhibitors were added to live keratinocytes during the production of tryptic KLKs, this treatment indirectly resulted in decreased TLSP activity. Furthermore, doxycycline under these conditions inhibited the generation of the cathelicidin peptide LL-37 from its precursor protein hCAP18, a process dependent on KLK activity. These results demonstrate that doxycycline can prevent cathelicidin activation, and suggest a previously unknown mechanism of action for doxycycline through inhibiting generation of active cathelicidin peptides.
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What OpenQuestion holds
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.