Doxycycline can deactivate Cathelicidins

Written by on February 21, 2012 in research, What Causes Rosacea? with 4 Comments

A recently published abstract from the house of Gallo suggests a clue as to how doxycycline might work in treating rosacea. The suggestion from this research is that doxycycline has a newly discovered mechanism of action whereby it is able to prevent the activation of cathelicidin.

Cathelicidin has been in the rosacea news since around 2002, gaining publicity because of the discoveries like the fact that rosacea sufferers have abnormally high levels of cathelicidin in their facial skin.

Previous research has also attempted to explain how Finacea works in rosacea as well as understanding how metrogel works.

Doxycycline Indirectly Inhibits Proteolytic Activation of Tryptic Kallikrein-Related Peptidases and Activation of Cathelicidin.

J Invest Dermatol. 2012 Feb 16.

Kanada KN, Nakatsuji T, Gallo RL.

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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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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4 Reader Comments

  1. i have just gone back on doxy(50 mg) because without it my skin wasn”t great! good to know this. actually i think doxy is better for me than metrogel,finacea, or the new expensive one for redness.

  2. Is doxycycline a cream or an antibiotic tablet

    • Stuart says:

      Doxycycline is an antibiotic tablet, which you can get on a private prescription, it cost around £26 for a months supply. You can get Oxytetracycline which does the same thing from your doctor for the price of a NHS prescription.( free in Scotland. ) If you are suffering from redness and itching from rosacea the tablets should help. You may also want to try a mild steroid cream like hydrocortisone or( Daktacort available from your doctor.) Best thing for spots relating to rosacea is Soolantra which has just become available on the NHS.

  3. KatCèe says:

    Oh no you dont….NO HYDROCORTISONE! That is a no no.

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