title: Endoplasmic reticulum stress and its regulator XBP-1 contributes to dendritic cell maturation and activation induced by high mobility group box-1 protein.
abstract: High mobility group box-1 protein (HMGB1) had been proved to induce maturation and activation of dendritic cell (DC), however, the endogenous changes and mechanisms underlying are unknown. Since endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular survival and repair, we hypothesized that HMGB1 may regulate the function of DC by modulating ERS. In our study, HMGB1 stimulation induced significant ERS responses in DCs in a time- and dose-dependent manner, demonstrated by the up-regulation of a number of ERS markers. Gene silence of XBP-1 in splenic DCs decreased the levels of CD80, CD86 as well as major histocompatibility complex (MHC)-II expression and cytokine secretion after HMGB1 treatment, when compared with untransfected or nontargeting-transfected DCs (all P<0.05). Moreover, XBP-1 silenced DCs after treatment with HMGB1 failed to stimulate notable proliferation and differentiation of T cells, unlike normal DCs or nontargeting-transfected DCs (all P<0.05). Gene silence of XBP-1 resulted in down-regulation of the receptor for advanced glycation end products (RAGE) expression on the surface of splenic DCs induced by HMGB1 stimulation (P<0.05). These findings demonstrate an important role for ERS and its regulator XBP-1 in HMGB1-induced maturation and activation of DCs.
authors.affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, PR China.
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Zhu
authors.forename: Feng-hua
authors.initials: FH
authors.lastname: Yao
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse