The effect of high mobility group box-1 protein on splenic dendritic cell maturation in rats.
High mobility group box-1 protein (HMGB1), a recently described late-acting cytokine that mediates lethality of sepsis and systemic inflammation, also plays a role in mediating dendritic cell (DC) maturation and activation. The present study was performed to clarify the effects of HMGB1 on splenic DCs and its potential regulating mechanism underlying T-cell-mediated immunity. DCs isolated from the spleens of normal rats were treated with HMGB1 of different dosage (0.1, 1, or 10 microg/mL) for different duration (24, 48, or 72 h). Expressions of co-stimulatory molecules, including CD80, CD86, and MHC-II on DCs surface, and cytokines, including interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, were analyzed to identify DCs maturation and activation. The activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. Expression of the receptor for advanced glycation end products (RAGE) on DCs and nuclear factor (NF)-kappaB activation in T lymphocytes were also determined. Stimulation with HMGB1 markedly up-regulated the co-stimulatory molecules and cytokines expressions, and they peaked at 48 h when DCs was treated with 1 microg/mL HMGB1. Treatment with anti-RAGE antibody prevented the maturation of DCs. DCs treated with HMGB1 (1 microg/mL for 48 h) promoted T-cell proliferation as well as differentiation, and markedly up-regulated IL-2, IL-2R expression and intranuclear NF-kappaB activation. The results suggested that HMGB1 appear to be a potential immunostimulatory signal that induced DC maturation and T-cell-mediated immunity, and RAGE was a potential receptor associated with maturation and differentiation of DCs. Moreover, HMGB1 might have a dual regulatory effect on immune functions of DCs varying with different concentration and stimulation time.
Zhu
Xiao-mei
XM
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China.
Yao
Yong-ming
YM
Liang
Hua-ping
HP
Xu
Shan
S
Dong
Ning
N
Yu
Yan
Y
Sheng
Zhi-yong
ZY
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D024243:HMGB1 Protein; D007376:Interleukin-2; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha