title: Human recombinant heat shock protein 70 affects the maturation pathways of dendritic cells in vitro and has an in vivo adjuvant activity.
abstract: Heat shock proteins (HSPs) are potent inducers of an antigen-specific immunological response. A role of chaperon of immunogenic peptides and a direct effect on APC activation and function have been described. However, the signal transduction events involved in the activation of human APCs are poorly characterized. We investigated, using human monocyte-derived dendritic cells (DCs), the signal transduction pathways activated by a human recombinant HSP70 (r)HSP70 purified from eukaryotic cells. rHSP70 effectively induced a partial maturation of DCs in vitro and a significant increase in the titers of antigen-specific IgG when used as a vaccine adjuvant in vivo. rHSP70 did not desensitize human DCs to LPS stimulation and retained its adjuvant properties in C3H/HeJ mice, which are LPS-resistant as a result of a mutation in TLR-4, ruling out the potential interference of LPS contamination. Effects on DC maturation and in vivo functions correlate to the ability of rHSP70 to activate IkappaB-alpha/NF-kappaB and ERK1/2 pathways in human DCs. No activation of p38 was induced in the same experimental conditions. Our data suggest that the IkappaB-alpha/NF-kappaB pathway has a critical role in the partial maturation of DCs induced by rHSP70.
authors.affiliation: Molmed S.p.A., via Olgettina 58, 20132 Milan, Italy. barbara.valentinis@molmed.com
authors.forename: Barbara
authors.initials: B
authors.lastname: Valentinis
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capobianco
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bianchi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens; D002454:Cell Differentiation / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins