Ll37

Antimicrobial peptide (AMP) of the cathelicidin family(porins). LL37 is the only cathelicidin antimicrobial peptide produced by humans. It is encoded by the CAMP gene (acronym for cathelicidin antimicrobial peptide) located on chromosome 3. LL37 is produced mainly in immune cells and is part of the innate immune system.

The biosynthesis of LL37 proceeds in several stages. Initially, a biologically inactive precursor is synthesized, a propetide that is stored in the granules of neutrophil granulocytes. After release of the propeptide, it is enzymatically cleaved by proteinases (e.g. elastases) into cathelin and the antimicrobial peptide LL37. Long wavelength light (630 and 940nm) suppresses the synthesis of LL37.

Cathelicidin LL37 affects Toll-like receptors as well as transactivation of "epidermal growth factor" ( EGF receptor). These properties characterize LL37 as a prototype alarmin (see antimicrobial peptides below) in the skin's defense against infection. LL37 complexes with DNA in the cytosol of keratinocytes, thereby neutralizing their action as a danger signal for the inflammasome AIM2.

LL37 can activate both CD4+ T helper cells and CD8+ cytotoxic cells. It has broad significance in inflammatory pathogenetic pathways (e.g. psoriasis, the systemic scleroderma). In psoriasis, LL-37 is upregulated. In wound healing, the antimicrobial potency of LL37 is used for local therapy by binding it in encapsulated form to nanoparticles. Furthermore, it plays a role in angiogenesis. LL37 is recognized by the immune system after binding to HLA-C*06:02. This underlines the importance of certain HLA genotypes for the pathogenesis of psoriasis (probably also for other inflammatory scenarios). Vitamin D analogues and vitamin D (UV irradiation) increase the synthesis of LL37 (antipsoriatic effect?).

Cathelicidin LL37 (as a product of infiltrating neutrophils) and autoantibodies to LL37 have been shown to be increased in psoriatic arthritis. Anti-LL37 antibodies correlate with clinical markers of inflammation. Anti-carbamylated-LL37 antibodies in plasma correlate with disease activity of PsA (DAS44) but not psoriasis (PASI) (Frasca L et al. 2018).

The name LL is derived from the first two letters of the 37-part one-letter code beginning with LL (see Syn).

1. Frasca L et al (2018) Anti-LL37 Antibodies Are Present in Psoriatic Arthritis (PsA) Patients: New Biomarkers in PsA. Front Immunol 9:1936.
2. Garcia-Orue I et al. (2016) LL37 loaded nanostructured lipid carriers (NLC): A new strategy for the topical treatment of chronic wounds.Eur J Pharm Biopharm doi: 10.1016/j.ejpb.2016.04.006.
3. Lee JB et al.(2016) Light Emitting Diodes Down-regulates Cathelicidin, Kallikrein, and Toll-like Receptor 2 Expressions in Keratinocytes and Rosacea-like Mouse Skin. Exp Dermatol doi: 10.1111/exd.13133.
4. Takahashi T et al. (2016) A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis. Br J Dermatol doi: 10.1111/bjd.14699.