title: Synergistic effect of muramyl dipeptide with heat shock protein 70 from Mycobacterium tuberculosis on immune activation.
abstract: Heat shock protein 70 from Mycobacterium tuberculosis (Mtb Hsp70) has been known to modulate immune response including dendritic cell activation. Muramyl dipeptide (MDP) is an immunoreactive derivative of peptidoglycan from all Gram-negative and Gram-positive bacteria and recognized to be responsible for function of Freund's complete adjuvant. In this study, we evaluated effect of MDP on in vitro activation of bone marrow derived dendritic cells (BMDCs) and in vivo production of cytokines and chemokines induced by Mtb Hsp70. MDP treatment with Mtb Hsp70 dramatically increased production of IL-6, IL-12p40 and TNF-α in BMDCs compared with Mtb Hsp70 alone whereas these effects were abolished in Nod2-deficient BMDCs. Phosphorylation of IκB-α and ERK and impairment of phagocytosis, which is an indicator of DC maturation were enhanced by MDP co-treatment with Mtb hsp70 in BMDCs. In addition, ability of Mtb Hsp70-stimulated BMDCs to induce IFN-γ productions of T cells was increased by MDP co-treatment. Finally, intraperitoneal injection of MDP with Mtb Hsp70 dramatically increased production of IL-6, CXCL-1 and CCL2 in serum compared with Mtb hsp70 injection. Our study showed the synergistic effects of MDP with Mtb Hsp70 on DCs and in vivo immune activation. The use of MDP with Mtb Hsp70 to induce immune activation may provide an effective strategy for vaccination to treat cancer and protect against pathogens.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul University, Seoul 151-742, Republic of Korea; BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Republic of Korea.
authors.forename: Tae-Hyoun
authors.initials: TH
authors.lastname: Kim
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Ryu
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004705:Endocytosis / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D016328:NF-kappa B; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D048049:Extracellular Signal-Regulated MAP Kinases