Abstract
Chemerin, a chemoattractant ligand for chemokine-like receptor 1 (CMKLR1) is predicted to share similar tertiary structure with antibacterial cathelicidins. Recombinant chemerin has antimicrobial activity. Here we show that endogenous chemerin is abundant in human epidermis, and that inhibition of bacteria growth by exudates from organ cultures of primary human skin keratinocytes is largely chemerin-dependent. Using a panel of overlapping chemerin-derived synthetic peptides, we demonstrate that the antibacterial activity of chemerin is primarily mediated by Val66-Pro85, which causes direct bacterial lysis. Therefore, chemerin is an antimicrobial agent in human skin.
Highlights
Chemerin is a multifunctional protein implicated in chemotaxis of immune cells, regulation of differentiation and metabolic function of adipocytes, and glucose homeostasis [1,2,3]
The highly positively-charged chemerin domain Val66-Pro85 embodies the majority of the anti-microbial activity, which is comparable in potency to other antimicrobial proteins
In this work we show that chemerin fragment Val66-Pro85 (p4) recapitulates the activity of longer chemerin isoforms such as chemS157, which are already devoid of the inhibitory C-term peptide
Summary
Chemerin is a multifunctional protein implicated in chemotaxis of immune cells, regulation of differentiation and metabolic function of adipocytes, and glucose homeostasis [1,2,3]. It binds with high affinity to three receptors, chemokine-like receptor 1 (CMKLR1) and atypical chemokine CC motif receptor-like 2 (CCRL2) as well as G protein-coupled receptor 1 (GPR1). Among these receptors, only CMKLR1 is responsible for direct chemerin-mediated chemotactic effects [4,5]. Chemerin mRNA is present in many tissues, including liver, fat, placenta, pancreas, lung and skin [6,7]. The liver may be a primary source for circulating blood chemerin [3]. Chemerin is expressed by epithelial cells, including kertinocytes [8], the biological significance of chemerin in skin remains unknown
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