Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.
High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP.
Department of Dermatovenereology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Department of Dermatovenereology, Chengdu second people's hospital, Chengdu, Sichuan, China.
Tao
T
Chen
Zai-Pei
ZP
Guo
Wen-Ju
WJ
Wang
Sha
S
Qin
Na
N
Cao
Meng-Meng
MM
Li
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D024243:HMGB1 Protein / Q000097:blood* / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D011695:IgA Vasculitis / Q000097:blood* / Q000209:etiology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014581:Urticaria / Q000097:blood; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
Henoch-Schönlein purpura; High-mobility group box-1; cytokine; endothelial cells