Abstract: Cathelicidin antimicrobial protein, hCAP18, is the sole cathelin protein in human. Its C-terminal peptide, which is released enzymatically from the holoprotein, has broad antimicrobial activity but also has effects on eukaryotic cells. hCAP18 is present in leukocytes and is produced at epithelial interfaces as part of the innate immune system. In normal intact skin, there is low constitutive expression of hCAP18, which is rapidly upregulated upon injury. Accumulating evidence indicates that hCAP18/LL-37 may serve a key role in protecting the integrity of the epithelium and also actively promote re-epithelialization and tissue repair. Molecular mechanisms responsible for controlling hCAP18 gene expression in vivo are only partly understood. Vitamin D3 and its analogue calcipotriol were recently found to directly induce transcription of the hCAP18 gene via functional vitamin D responsive elements in the hCAP18 gene promoter.
Skin is the major source for vitamin D3 in human, where its production is dependent on ultraviolet B (UVB) radiation. We have shown that exposure to UVB, sufficient to produce vitamin D3, upregulates hCAP18 in human skin in vivo. In the present study, we demonstrate that the upregulation of hCAP18/LL-37 following acute skin injury is further enhanced, at both hCAP18 mRNA and protein levels, after topical treatment with the vitamin D3 analogue calcipotriol. In chronic ulcers, calcipotriol treatment upregulated hCAP18 mRNA, whereas no consistent upregulation of hCAP18 protein was detected. Our results further support the role of vitamin D3 as a key physiologic regulator of hCAP18/LL-37 in human skin.
(Fonte: Experimental Dermatology, Volume 19 Issue 4, Pagg 332 – 338)
Dr.ssa Adele Sparavigna
Specialista in Dermatologia e Venereologia