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If you were around in August 2007, there were headlines such as, Scientists unmask the cause of rosacea, [1] and UCSD Researchers Discover Cause of Rosacea [2] not to mention all the other headlines which created quite a stir in all the online rosacea groups and brought a lot of hope for rosacea sufferers. These articles seemed to conclude that rosacea’s mystery is resolved and within time a treatment would be found to eradicate rosacea. These startling headlines were the result of a paper published by researchers at UCSD associated with Richard L Gallo, et.al, in a study published by Nature Medicine [3]. This paper concluded:

“These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease.” 

If you will notice in the above statement that the findings suggest an explanation for the pathogenesis of rosacea. Gallo, et.al, never said they found the cause of rosacea. The newspapers came to the conclusion that now all the mystery of rosacea is over and we now have the cause nailed down. All we have to do is wait for the treatment. This is not exactly the truth. While the research of Gallo, et.al, at UCSD is remarkable and insightful, the jury is still out on what causes rosacea. And while the jury is still out, there is more news worth mentioning that may be related to cathelicidin, peptides or antigenic proteins.

You might want to read this thread on Gallo's research.

You may also view a Medscape video lecture by Dr. Gallo, New Insights Into the Science of Treating Rosacea, where he discusses the innate immunity and cathelicindin.

An interesting read if you understand this subject well is an article published in Antimicrobial Agents and Chemotherapy, entitled, Degradation of Human Antimicrobial Peptide LL-37 by Staphylococcus aureus-Derived Proteinases. [4]

What Does Cathelicidin Have To Do With Rosacea?

Wikipedia in its article on Cathelcidin says, "Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs), and keratinocytes."

After reading the above, this is where we meager uneducated rosacea sufferers start to yawn, get lost, or say 'who cares?' So get on your thinking caps and follow with me.

Cathelicidin is a peptide.  Antimicrobial Peptides (AMPs), "also called host defense peptides (HDPs) are part of the innate immune response found among all classes of life." Wikipedia

"Peptides (from Gr.: πεπτός, peptós "digested"; derived from πέσσειν, péssein "to digest") are biologically occurring short chains of amino acid monomers linked by peptide (amide) bonds." Wikipedia If you forgot what amino acid monomers are, amino acids are the building blocks of protein and make up the 'the second-largest component (water is the largest) of human muscles, cells and other tissues." Wikipedia "A monomer (/ˈmɒnəmər/ mon-ə-mər[1]) (mono-, "one" + -mer, "part") is a molecule that may bind chemically or supramolecularly to other molecules." Wikipedia

So breaking this down, Cathelicidin is related to a family of anti-microbial (an antimicrobial is an agent that kills microorganisms or inhibits their growth) peptides (short chains of amino acids) found in lysomes (a membrane-bounded organelle [a specialized subunit within a cell that has a specific function] found in most animal cells) of macrophages (a type of white blood cell) and polymorphonuclear leukocytes (a category of white blood cells) and and keratinocytes (predominant cell type in the outermost layer of the skin).

The nutshell version is that Cathelicidin is a killer of microscopic organisms that is at the cellular level found in white blood cells and also found in cells on the skin. 

In the article in Nature magazine [3] the paper mentions that in rosacea patients the cathelicidin levels were abnormally high suggesting that the redness is caused by an abnormal immune system response. The conclusion of the article says, "These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease." [3] (Italics added)

"However, following injury or inflammatory skin diseases such as psoriasis and rosacea, expression of the cathelicidin antimicrobial peptide LL37 breaks tolerance to self-nucleic acids and triggers inflammation." [7]

"Dysregulation of the innate immune response increases the secretion of antimicrobial peptides (AMP) and cytokines, via activation of toll-like receptor 2 (TLR-2). The main AMP is cathelicidin, which is cleaved by kallikrein 5 (KLK-5) into the active peptide LL-37. This is the fundamental mediator for activating and controlling numerous processes: release of cytokines and metalloproteinases (MMP) by leukocytes, mast cells, and keratinocytes, regulation of the expression of extracellular matrix components, and increased proliferation of endothelial cells, causing angiogenesis. MMP-2 and MMP-9 are elevated on the skin of patients, exerting inflammatory, angiogenic, and dermal framework disruption functions in addition to helping in the activation of KLK-5, retrofeeding the system. MMP-9 is directly stimulated by the mite Demodex folliculorum (Df)." [8]

AMPs in Clinical Development

There is much excitement with using AMPs and ACPs in treating cancer. 

"As shown here, different microbial infections and/or cancer-targeting peptides are in clinical trials, with approval for clinical application expected for the next few years (at least 10 in the next 5 years). Moreover, that number should tend to increase due to advances in the rational design of peptides, minimizing or eliminating cytotoxic effects. In addition, advances in the large-scale synthesis of peptides has made this process cheaper, thus making peptide-based therapies likely to become more accessible to patients." [5]

Associated Diseases
"In addition, the association between cardiovascular diseases and rosacea might also be explained by enhanced expression of the cathelicidin, which has been observed both in the course of atherosclerosis and rosacea." [6]

Independent Rosacea Research
Could a group of rosacea sufferers in a non profit organization like the RRDi collectively get together and sponsor their own research on rosacea? For example, if 10K members each donated a dollar, could it be possible that this money could be used to sponsor their own independent rosacea research on a cathlecidin?  What do you think? If you want to do something about this read this post


All this started due to Gallo, et al, in 2007 and we continue to watch for more developments. 


Rosacea Theories Revisited.

Other Cytokines to Consider

Reply to this Topic
There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post?  And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register?  We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post.  

End Notes

[1] Scientists unmask the cause of rosacea
August 06, 2007 | Alison Williams, Los Angeles Times Staff Writer

[2] UCSD Researchers Discover Cause of Rosacea
UCSD News Center

[3] Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea
Kenshi Yamasaki, Anna Di Nardo, Antonella Bardan, Masamoto Murakami, Takaaki Ohtake, Alvin Coda, Robert A Dorschner, Chrystelle Bonnart, Pascal Descargues, Alain Hovnanian, Vera B Morhenn & Richard L Gallo
Nature Medicine 13, 975 – 980 (2007)
Published online: 5 August 2007 | doi:10.1038/nm1616

[4] Antimicrob Agents Chemother. 2004 December; 48(12): 4673–4679.
doi: 10.1128/AAC.48.12.4673-4679.2004
PMCID: PMC529204
Degradation of Human Antimicrobial Peptide LL-37 by Staphylococcus aureus-Derived Proteinases
Magdalena Sieprawska-Lupa, Piotr Mydel, Katarzyna Krawczyk, Kinga Wójcik, Magdalena Puklo, Boguslaw Lupa, Piotr Suder, Jerzy Silberring, Matthew Reed, Jan Pohl, William Shafer, Fionnuala McAleese, Timothy Foster, Jim Travis, and Jan Potempa

[5] Front Chem. 2017; 5: 5.
Published online 2017 Feb 21. doi:  10.3389/fchem.2017.00005
PMCID: PMC5318463
Peptides with Dual Antimicrobial and Anticancer Activities
Mário R. Felício, Osmar N. Silva, Sônia Gonçalves, Nuno C. Santos, and Octávio L. Franco

[6] Int J Mol Sci. 2016 Sep; 17(9): 1562.
Published online 2016 Sep 15. doi:  10.3390/ijms17091562, PMCID: PMC5037831
Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition
Yu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park

[7] Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors.
Sci Rep. 2018 Mar 05;8(1):4032
Takahashi T, Kulkarni NN, Lee EY, Zhang LJ, Wong GCL, Gallo RL

[8] An Bras Dermatol. 2020 Nov-Dec; 95(Suppl 1): 53–69.
Consensus on the therapeutic management of rosacea – Brazilian Society of Dermatology
Clivia Maria Moraes de Oliveira, Luiz Mauricio Costa Almeida, Renan Rangel Bonamigo, Carla Wanderley Gayoso de Lima, Ediléia Bagatinf

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