title: High-mobility group box-1 induces proinflammatory cytokines production of Kupffer cells through TLRs-dependent signaling pathway after burn injury.
abstract: Kupffer cells (KCs) were a significant source of cytokine release during the early stage of severe burns. High mobility group box protein 1 (HMGB1) was recently identified as a new type of proinflammatory cytokine. The ability of HMGB1 to generate inflammatory responses after burn trauma has not been well characterized. KCs were isolated from sham animals and rats with a 30% full-thickness burn, and then were stimulated with increasing concentrations of HMGB1. The levels of Tumor necrosis factor (TNF)-α and interleukin (IL)-1β in culture supernatant were measured by enzyme-linked immunosorbent assay. Northern blot analysis was performed to detect the expressions of TNF-α and IL-1β mRNAs. The activities of p38 MAPK and JNK (by Western blot analysis) as well as NF-κB (by EMSA) in KCs were also examined. As a result, HMGB1 in vitro upregulated expressions of TNF-α and IL-1β of KCs in a dose-dependent manner, and HMGB1 promoted KCs from burn rats to produce significantly more TNF-α and IL-1β proteins than those from sham animals. After harvested from burn rats, KCs were pre-incubated with anti-TLR2 or anti-TLR4 antibody prior to HMGB1 administration. HMGB1 exposure not only significantly increased expressions of TNF-α and IL-1β mRNAs in KCs from burn rats, but also enhanced activities of p38 MAPK, JNK and NF-κB. However, these upregulation events were all reduced by pre-incubation with anti-TLR2 or anti-TLR4 antibody. These results indicate that HMGB1 induces proinflammatory cytokines production of KCs after sever burn injury, and this process might be largely dependent on TLRs-dependent MAPKs/NF-κB signal pathway.
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China. okcxl@126.com
authors.forename: Xu-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Xun
authors.initials: X
authors.lastname: Liang
authors.forename: Ren-Su
authors.initials: RS
authors.lastname: Wang
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ye-Xiang
authors.initials: YX
authors.lastname: Sun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D002056:Burns / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D024243:HMGB1 Protein / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha