Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea

Abstract

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 telangiectasia. 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 peptides. 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.

Blushing in rosacea sufferers

“…Yamasaki and Gallo [25] proposed recently that the innate immune system triggers an abnormal inflammatory reaction that mediates the symptoms of rosacea [26,27]. If so, erythema may be due to chronic inflammation.…”

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

“…Excessive LL-37 is associated with rosacea and drives inflammation and abnormal blood vessel growth through cell activation mechanisms (Yamasaki et al, 2007). The high levels of LL-37 in psoriasis may also promote undesirable inflammation (Gilliet and Lande, 2008).…”

Avaliação Psicológica em Doentes com Rosácea: Um Estudo de Caso-Controlo com Symptom Checklist -90 - Revised

“…[31][32][33] In short, it is believed that whatever the nature of the stimulus -emotional, environmental, microbiological, immunological…-frequent and repeated blushing may lead, on the long term, to a permanent loss of the skin vascular tone, as such resulting in erythema and oedema of the tissues, 34 further aggravated by actinic damage of the dermal connective tissue and the ensuing loss of supportive strength to the vasculature walls. 35 The way these classic and new pathogenic data (namely on the role of the disturbed innate immunity and systemic cardiovascular comorbidities) [36][37][38][39] relate with the clinical evidence on rosacea patients` personality and psychism is a matter still under debate and investigation. The fact remains that ROS patients are usually said to be anxious or phobic, with obsessive traits or disorder and, accordingly, their lives are compromised by self-consciousness, social anxiety and avoidance.…”