Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease

Abstract

Chronic inflammatory skin diseases such as atopic dermatitis, psoriasis or rosacea are very common. Although their exact pathogenesis is not completely understood all three diseases are characterized by dysregulation of cutaneous innate immunity. Cathelicidin LL-37 is an important effector molecule of innate immunity in the skin and atopic dermatitis, psoriasis or rosacea show defects in cathelicidin expression, function or processing. In atopic dermatitis, cathelicidin induction might be disturbed resulting in defective antimicrobial barrier function. In contrast, psoriasis is characterized by overexpression of cathelicidin. However to date it is unclear whether pro- or anti-inflammatory functions of cathelicidin predominate in lesional skin in psoriasis. In rosacea, cathelicidin processing is disturbed resulting in peptide fragments causing inflammation, erythema and telangiectasias. In this review, the current evidence on the role of cathelicidin LL-37 in the pathogenesis of inflammatory skin diseases will be outlined. As cathelicidin LL-37 might also serve as a future treatment target potential novel treatment strategies for those diseases will be discussed.

Keywords: Atopic dermatitis; Cathelicidin LL-37; Innate immunity; Psoriasis; Rosacea; Vitamin D.

Fig. 1

The role of cathelicidin in the pathogenesis of rosacea and possible therapeutic implications. UV light increases the synthesis of vitamin D which induces cathelicidin expression in keratinocytes. ER stress is an alternative inducer of cathelicidin production. Increased protease activity in rosacea skin is possibly due to demodex mite colonization: Chitin released from mites triggers TLR2 receptor activation and increased protease activity. Subsequently, enhanced protease activity leads to increased cleavage of cathelicidin LL-37 and further fragments. These fragments trigger inflammation, erythema and telangiectasias. Doxycycline, azelaic acid and retinoids mediate their beneficial effects in rosacea possibly by interfering with this pro-inflammatory system through different mechanisms. UV: ultraviolet, ER: endoplasmic reticulum, TLR: Toll-like receptor.