title: Regulation of chemerin chemoattractant and antibacterial activity by human cysteine cathepsins.
abstract: Chemerin, a ligand for the G-protein coupled receptor chemokine-like receptor 1, requires C-terminal proteolytic processing to unleash its chemoattractant activity. Proteolytically processed chemerin selectively attracts specific subsets of immunoregulatory APCs, including chemokine-like receptor 1-positive immature plasmacytoid dendritic cells (pDC). Chemerin is predicted to belong to the structural cathelicidin/cystatin family of proteins composed of antibacterial polypeptide cathelicidins and inhibitors of cysteine proteinases (cystatins). We therefore hypothesized that chemerin may interact directly with cysteine proteases, and that it might also function as an antibacterial agent. In this article, we show that chemerin does not inhibit human cysteine proteases, but rather is a new substrate for cathepsin (cat) K and L. cat K- and L-cleaved chemerin triggered robust migration of human blood-derived pDC ex vivo. Furthermore, cat K- and L-truncated chemerin also displayed antibacterial activity against Enterobacteriaceae. Cathepsins may therefore contribute to host defense by activating chemerin to directly inhibit bacterial growth and to recruit pDC to sites of infection.
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kulig
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kantyka
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
authors.forename: Magdalena
authors.initials: M
authors.lastname: Banas
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chyra
authors.forename: Anna
authors.initials: A
authors.lastname: Stefanska
authors.forename: Hua
authors.initials: H
authors.lastname: Tu
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.forename: Joanna
authors.initials: J
authors.lastname: Cichy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood*; D016466:CHO Cells; D002401:Cathepsin B / Q000502:physiology*; D056657:Cathepsin K / Q000502:physiology*; D056668:Cathepsin L / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000097:blood*; D002630:Chemotactic Factors / Q000097:blood*; D006224:Cricetinae; D003412:Cricetulus; D057056:Cysteine Proteases / Q000097:blood*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D019707:Receptors, Chemokine / Q000097:blood*; D011994:Recombinant Proteins / Q000097:blood; D013379:Substrate Specificity / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; C102741:CMKLR1 protein, human; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D057056:Cysteine Proteases; D002401:Cathepsin B; D056668:Cathepsin L; D056657:Cathepsin K