Dendritic cell activating peptides induce distinct cytokine profiles.
High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic protein, is a pro-inflammatory cytokine released by monocytes and macrophages. HMGB1 as well as its B box domain induce maturation of human dendritic cells (DCs). This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1beta, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, but not IL-6 and IL-10. Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1beta, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs. Interestingly, these peptides differed in their capacity to induce TNF-alpha, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T cells. These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs.
Telusma
Gloria
G
The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
Datta
Sandip
S
Mihajlov
Ivan
I
Ma
Wenxue
W
Li
Jianhua
J
Yang
Huan
H
Newman
Walter
W
Messmer
Bradley T
BT
Minev
Boris
B
Schmidt-Wolf
Ingo G H
IG
Tracey
Kevin J
KJ
Chiorazzi
Nicholas
N
Messmer
Davorka
D
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*
D016207:Cytokines; D024243:HMGB1 Protein; D010455:Peptides