Acne rosacea is an inflammatory skin disease that affects 3% of the US population over 30 years of age and is characterized by erythema, papulopustules and telangiectasia1,2,3. The etiology of this disorder is unknown, although symptoms are exacerbated by factors that trigger innate immune responses, such as the release of cathelicidin antimicrobial peptides4. Here we show that individuals with rosacea express abnormally high levels of cathelicidin in their facial skin and that the proteolytically processed forms of cathelicidin peptides found in rosacea are different from those present in normal individuals. These cathelicidin peptides are a result of a post-translational processing abnormality associated with an increase in stratum corneum tryptic enzyme (SCTE) in the epidermis. In mice, injection of the cathelicidin peptides found in rosacea, addition of SCTE, and increasing protease activity by targeted deletion of the serine protease inhibitor gene Spink5 each increases inflammation in mouse skin. The role of cathelicidin in enabling SCTE-mediated inflammation is verified in mice with a targeted deletion of Camp, the gene encoding cathelicidin. 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.
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We thank B. Cottrell for instructions in SELDI-TOF-MS analysis. This work was supported by the National Institutes of Health (R01-AI052453, R01-AR45676), The National Rosacea Society and a VA Merit Award (R.L.G.); and the Association for Preventive Medicine of Japan (K.Y.).
The authors declare no competing financial interests.
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Yamasaki, K., Di Nardo, A., Bardan, A. et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 13, 975–980 (2007). https://doi.org/10.1038/nm1616
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