title: Role of PKC-β in chemical allergen-induced CD86 expression and IL-8 release in THP-1 cells.
abstract: We previously demonstrated an age-related decrease in receptor for activated C-kinase (RACK-1) expression and functional deficit in Langerhans cells' responsiveness. This defect specifically involves the translocation of protein kinase C (PKC)-β. The purpose of this study was to investigate the role of RACK-1 and PKC-β in chemical allergen-induced CD86 expression and IL-8 release in the human promyelocytic cell line THP-1 and primary human dendritic cells (DC). Dinitrochlorobenzene, p-phenylenediamine and diethyl maleate were used as contact allergens. The selective cell-permeable inhibitor of PKC-β and the broad PKC inhibitor GF109203X completely prevented chemical allergen- or lipopolysaccharide (LPS)-induced CD86 expression and significantly modulated IL-8 release (50 % reduction). The selective cell-permeable inhibitor of PKC-ε (also known to bind to RACK-1) failed to modulate allergen- or LPS-induced CD86 expression or allergen-induced IL-8 release, while modulating LPS-induced IL-8 release. The use of a RACK-1 pseudosubstrate, which directly activates PKC-β, resulted in dose-related increase in CD86 expression and IL-8 release. Similar results were obtained with human DC, confirming the relevance of results obtained in THP-1 cells. Overall, our findings demonstrate the role of PKC-β and RACK-1 in allergen-induced CD86 expression and IL-8 production, supporting a central role of PKC-β in the initiation of chemical allergen-induced DC activation.
authors.affiliation: Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Università degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy, emanuela.corsini@unimi.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.forename: Valentina
authors.initials: V
authors.lastname: Galbiati
authors.forename: Philipp R
authors.initials: PR
authors.lastname: Esser
authors.forename: Antonella
authors.initials: A
authors.lastname: Pinto
authors.forename: Marco
authors.initials: M
authors.lastname: Racchi
authors.forename: Marina
authors.initials: M
authors.lastname: Marinovich
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Martin
authors.forename: Corrado L
authors.initials: CL
authors.lastname: Galli
mesh_terms: D000485:Allergens / Q000276:immunology / Q000633:toxicity*; D051940:B7-2 Antigen / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects*; D004137:Dinitrochlorobenzene / Q000276:immunology / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008298:Maleates / Q000276:immunology / Q000633:toxicity; D008301:Maleimides / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010655:Phenylenediamines / Q000276:immunology / Q000633:toxicity; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000485:Allergens; D051940:B7-2 Antigen; C497964:CD86 protein, human; D004137:Dinitrochlorobenzene; D004791:Enzyme Inhibitors; D007211:Indoles; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008298:Maleates; D008301:Maleimides; D009363:Neoplasm Proteins; D010655:Phenylenediamines; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D064546:Protein Kinase C beta; D019204:GTP-Binding Proteins; C014476:diethyl maleate; C070515:bisindolylmaleimide I; C029728:4-phenylenediamine