Increased serum HMGB1 levels in patients with Henoch–Schönlein purpura

Abstract

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.

Involvement of high mobility group box‐1 in imiquimod‐induced psoriasis‐like mice model

“…had reported that the mitogenic and chemotactic activities of HMGB1 can be inhibited by glycyrrhizin. Also, glycyrrhizin can bind directly to HMGB1 protein and confirm its binding site . Additionally, glycyrrhizin has been recognized as a HMGB1 inhibitor and potentially blockade the extracellular release of HMGB1 from the cell nucleus .…”

“…Also, glycyrrhizin can bind directly to HMGB1 protein and confirm its binding site. 23,24 Additionally, glycyrrhizin has been recognized as a HMGB1 inhibitor and potentially blockade the extracellular release of HMGB1 from the cell nucleus. 15,25 In East Asia, glycyrrhizin has been recognized as a natural anti-inflammatory agent and now extensively used for the treatment of various inflammatory skin diseases including psoriasis.…”

A pilot study of oral tranexamic acid and Glycyrrhizin compound in the treatment of recalcitrant Riehl’s melanosis

“…Notably, HMGB1 has been well recognized as an important signaling molecule involved in both acute and chronic inflammation process . Its expression was significantly increased in a variety of skin diseases, such as psoriasis, alopecia areata, vitiligo, atopic dermatitis, Henoch‐Schönlein purpura (HSP), pemphigus, and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS) . Due to the similar pharmacological efficacy to corticosteroids but with milder side effects, Glycyrrhizin has been widely utilized in several dermatologic disorders for many years, such as active‐stage generalized vitiligo, psoriasis, alopecia areata, and is also reported to be effective in alleviating the symptoms of atopic dermatitis and systemic sclerosis in animal model .…”

The Anti-inflammatory Effects of HMGB1 Blockades in a Mouse Model of Cutaneous Vasculitis

“…It has been proven in our previous study that HMGB1 is involved in the pathogenesis of inflammatory and autoimmune disorders, such as, Henoch– Schonlein purpura (HSP), allergic vasculitis (AV), and urticarial vasculitis (UV). It also altered HMGB1 distribution in lesional skin in patients with HSP ( 11 – 13 ). However, the function and mechanism of HMGB1 in vasculitis has not been clearly stated.…”