LL37

Porins; Stratum corneum; Antimicrobial peptides; Skin barrier; AMP; Cathelicidin family;

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 occurs in several stages. Initially, a biologically inactive precursor is synthesized—a propeptide that is stored, among other places, in the granules of neutrophils. After the propeptide is released, it is enzymatically cleaved by proteases (e.g., elastases; or serine proteases such as kallikrein 5—see below, KLK5) into cathelin and the antimicrobial peptide LL37. Long-wavelength light (630 and 940 nm) suppresses the synthesis of LL37.

Cathelicidin LL37 influences Toll-like receptors as well as the transactivation of the epidermal growth factor receptor ( EGF receptor). These properties characterize LL37 as a prototypical alarmin (see below: antimicrobial peptides) in the skin’s defense against infection. In the cytosol of keratinocytes, LL37 forms a complex with DNA, thereby neutralizing its effect as a danger signal for the AIM2 inflammasome.

LL37 can activate both CD4+ T-helper cells and CD8+ cytotoxic cells. It plays a significant role in inflammatory pathogenic processes (e.g., psoriasis, systemic scleroderma).

In psoriasis, LL-37 is upregulated. In wound healing, the antimicrobial potency of LL37 is utilized in local therapy by binding it to nanoparticles in an encapsulated form. Furthermore, it plays a role in angiogenesis. LL-37 is recognized by the immune system after binding to HLA-C*06:02. This underscores the importance of certain HLA genotypes for the pathogenesis of psoriasis (and likely for other inflammatory conditions as well). Vitamin D analogs and vitamin D (UV irradiation) increase the synthesis of LL37 (antipsoriatic effect?).

It has been shown that the cathelicidin LL37 (produced by infiltrating neutrophils) and autoantibodies against LL37 are elevated in psoriatic arthritis. Anti-LL37 antibodies correlate with clinical markers of inflammation. Anti-carbamylated-LL37 antibodies in plasma correlate with disease activity in PsA (DAS44), but not in 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.