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By Hannah Sivak, PhD
Biochemist
Skin Actives Scientific
When your friend becomes your enemy (II): antimicrobial peptides
Cathelicidin antimicrobial peptides provide an important mechanism for prevention of infection against a wide variety of microbial pathogens. The activity of cathelicidin is controlled by the processing of a longer precursor into a mature peptide by a specific protease, i.e. a protein that breaks down proteins. In the skin, these peptides are formed when stratum corneum tryptic enzymes (SCTE) cut down cathelicidin at specific points.
In rosacea, cathelicidin and SCTE are much more abundant. The consequence is a massive increase in antimicrobial peptides that can be different in structure from those found in normal skin. The abnormal peptides are capable of producing rosacea-like symptoms: redness, an increase in visible blood vessels, bumps or pimples. Knowing that these peptides may be at the root of rosacea, it may seem easy to find a remedy and suppress the “celtic curse”: decrease the formation of the peptides. Unfortunately, the two processes involved, incrased expression of cathelicidin and increased expression of the SCTEs, cannot be easily modified.
What NOT to do if you have rosacea: vitamin D and retinoic acid seem to promote expression of cathelicidin, so people with rosacea should avoid these actives. Also, two growth factors are known to increase cathelicidin expression: insulin-like growth factor I and TGF-alpha, so run away if you see a skin care product (NOT made by SAS, obviously) that includes either factor in its ingredient list.
What else can you do? It may be possible to decrease the activity of the protease involved in the process, which belongs to a class known as serine protease because the amino acid serine is involved in the mechanism of action. Several actives sold by SAS inhibit serine proteases, including lupeol (present in saw palmetto), pumpkin fruit trypsin inhibitors, quercetin, and (maybe) betulinic acid. Also, protect your skin from infection and weakening of the skin barrier, to prevent further increase in the expression of cathelicidin.
Other skin problems seem to involve cathelicidin in different ways. For example, in atopic eczema the skin shows decreased cathelicidin expression, leading to increased susceptibility to secondary infections in those patients. In psoriasis, cathelicidin peptides may bind to self DNA, triggering an autoimmune response.
The skin is a complicated system, and proteases are needed for skin renewal, so although washing with a mild surfactant may help alleviate rosacea by decreasing activity of serine proteases, too much washing may be a problem.
Yamasaki, Kenshi; Di Nardo, Anna; Bardan, Antonella; Murakami, Masamoto; Ohtake, Takaaki; Coda, Alvin; Dorschner, Robert A.; Bonnart, Chrystelle; Descargues, Pascal; Hovnanian, Alain; Morhenn, Vera B.; Gallo, Richard L. (2007) Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea Nature Medicine 13(8), 975-980.
Biochemist
Skin Actives Scientific
When your friend becomes your enemy (II): antimicrobial peptides
Cathelicidin antimicrobial peptides provide an important mechanism for prevention of infection against a wide variety of microbial pathogens. The activity of cathelicidin is controlled by the processing of a longer precursor into a mature peptide by a specific protease, i.e. a protein that breaks down proteins. In the skin, these peptides are formed when stratum corneum tryptic enzymes (SCTE) cut down cathelicidin at specific points.
In rosacea, cathelicidin and SCTE are much more abundant. The consequence is a massive increase in antimicrobial peptides that can be different in structure from those found in normal skin. The abnormal peptides are capable of producing rosacea-like symptoms: redness, an increase in visible blood vessels, bumps or pimples. Knowing that these peptides may be at the root of rosacea, it may seem easy to find a remedy and suppress the “celtic curse”: decrease the formation of the peptides. Unfortunately, the two processes involved, incrased expression of cathelicidin and increased expression of the SCTEs, cannot be easily modified.
What NOT to do if you have rosacea: vitamin D and retinoic acid seem to promote expression of cathelicidin, so people with rosacea should avoid these actives. Also, two growth factors are known to increase cathelicidin expression: insulin-like growth factor I and TGF-alpha, so run away if you see a skin care product (NOT made by SAS, obviously) that includes either factor in its ingredient list.
What else can you do? It may be possible to decrease the activity of the protease involved in the process, which belongs to a class known as serine protease because the amino acid serine is involved in the mechanism of action. Several actives sold by SAS inhibit serine proteases, including lupeol (present in saw palmetto), pumpkin fruit trypsin inhibitors, quercetin, and (maybe) betulinic acid. Also, protect your skin from infection and weakening of the skin barrier, to prevent further increase in the expression of cathelicidin.
Other skin problems seem to involve cathelicidin in different ways. For example, in atopic eczema the skin shows decreased cathelicidin expression, leading to increased susceptibility to secondary infections in those patients. In psoriasis, cathelicidin peptides may bind to self DNA, triggering an autoimmune response.
The skin is a complicated system, and proteases are needed for skin renewal, so although washing with a mild surfactant may help alleviate rosacea by decreasing activity of serine proteases, too much washing may be a problem.
Yamasaki, Kenshi; Di Nardo, Anna; Bardan, Antonella; Murakami, Masamoto; Ohtake, Takaaki; Coda, Alvin; Dorschner, Robert A.; Bonnart, Chrystelle; Descargues, Pascal; Hovnanian, Alain; Morhenn, Vera B.; Gallo, Richard L. (2007) Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea Nature Medicine 13(8), 975-980.
Guide created: 05/10/08 (updated 05/10/08)
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