title: Cathepsin K inhibition renders equine bone marrow nucleated cells hypo-responsive to LPS and unmethylated CpG stimulation in vitro.
abstract: Cathepsin K (CatK) is an important enzyme regulating bone degradation and has been shown to contribute to the immune response. We have studied two inflammatory models in equine bone marrow nucleated cells (BMNCs); the LPS and the unmethylated CpG stimulation with the following objectives to: 1.determine whether CatK inhibition will alter the cytokine secretion by stimulated BMNCs; specifically IL-1β, IL-6, and TNF-α, and 2.determine the changes in BMNCs surface markers' expression and MHC II molecule under CatK inhibition. Cathepsin K inhibition promoted BMNCs viability and reduced cell apoptosis. Moreover, CatK inhibition significantly decreased cytokine secretion of either naïve or stimulated BMNCs, and altered their MHC II molecule expression. In conclusion, CatK inhibition in horses did affect BMNCs other than mature osteoclasts rendering them hypo-responsive to both TLR4- and TLR9-induced inflammation, predicting a proteolytic activity for CatK within the MyD88 pathway and/or the following proteolytic events required for the cytokines secretion.
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, United States.
authors.forename: Hayam
authors.initials: H
authors.lastname: Hussein
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, United States.
authors.forename: Prosper
authors.initials: P
authors.lastname: Boyaka
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dulin
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, United States; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, United States. Electronic address: Bertone.1@osu.edu.
authors.forename: Alicia
authors.initials: A
authors.lastname: Bertone
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology*; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology*; D005802:Genes, MHC Class II; D006736:Horses; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D015853:Cysteine Proteinase Inhibitors; D004852:Epoxy Compounds; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; C000599727:VEL-0230; D056657:Cathepsin K
keywords: Cytokine; Immune; Inflammation; Toll like receptor; VEL-0230