title: Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21, which inhibits pro-inflammatory responses to several pathogen-associated molecular patterns in vitro and in vivo by preventing toll-like receptor dimerization and subsequent activation of down-stream signalling pathways. Thus, P. aeruginosa 'hijacks' an endogenous anti-inflammatory peptide-based mechanism, thereby enabling modulation and circumvention of host responses.
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.
authors.forename: Mariena J A
authors.initials: MJ
authors.lastname: van der Plas
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.
authors.forename: Ravi K V
authors.initials: RK
authors.lastname: Bhongir
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, PO Box 124, Lund SE-22362, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Kjellström
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Siller
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Kasetty
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornavägen 10, Lund SE-22184, Sweden.|Dermatology and Venereology, Skane University Hospital, Lasarettsgatan 15, Lund SE-22185, Sweden.|Dermatology, LKCMedicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D050296:Microbial Viability; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D013917:Thrombin / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010455:Peptides; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D013917:Thrombin; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa