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

Abstract

In the previous work, we have indicated that HMGB1, a pro-inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)-induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis-like inflammation, and consecutively injected with recombinant HMGB1 or phosphate-buffered saline (PBS) i.d. Abundant cytoplasmic expression of HMGB1 was observed in lesional skin from IMQ-treated skin. The injection of HMGB1 into the IMQ-treated skin further aggravated the psoriasis-like disease, enhanced the infiltration of CD3 T cells, myeloperoxidase neutrophils and CD11c dendritic cells, increased the number of γδ T cells, and upregulated the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-17 compared with the PBS injection. Finally, by using anti-HMGB1 monoclonal antibody or HMGB1 inhibitor glycyrrhizin, we indicated that HMGB1 blockade reduced the number of γδ T cells, suppressed the mRNA expression of IL-6, TNF-α, IFN-γ and IL-17, and moderated clinical and histological evolvement in the IMQ-treated skin. Our data suggest that HMGB1 may act as a pro-inflammatory cytokine, and contribute to the development of IMQ-induced psoriasis-like inflammation. HMGB1 blockade may represent a new direction in the suppression of psoriasis.

Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma

“…Despite GL's anti-viral and anti-inflammatory effects, these two inhibitors displayed comparable in vitro and in vivo suppressive efficiencies in angiogenic activities. It was once again demonstrated that GL acts as a direct inhibitor of HMGB1 [48] and, consistent with a previous report [49], GL exerts similar effectiveness as anti-HMGB1 mAb. To the best of our knowledge, this report provides the first evidence that HMGB1 encountered within the TME closely interacts with B cells for the secretion of proangiogenic factors that promote angiogenesis.…”

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

“…It has been reported that glycyrrhizin can effectively inhibit the cytoplasmic transduction of HMGB1. Our previous studies also found that glycyrrhizin can target the inhibition of cytoplasmic transduction in HMGB1 and thus inhibit the expression of inflammatory cytokines, and it has been proven that glycyrrhizin is a direct inhibitor of HMGB1 ( 13 ). This study used glycyrrhizin to effectively treat vasculitis mice and reduce inflammation.…”

“…The high mobility group box 1 protein (HMGB1) is universal in all the cells of higher eukaryotes, is secreted by inflammatory cells (such as: activated monocytes, macrophages, mature dendritic cells, and natural killer cells), and may act as a potent mediator of inflammation ( 17 – 20 ). Our previous work found that the expression of HMGB1 was elevated in a variety of vasculitis diseases, and it was decreased in patients with HSP after treatment ( 13 ). HMGB1 may play an important role in the pathogenic mechanism of 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.…”

Advanced Characterization of Imiquimod-Induced Psoriasis-Like Mouse Model

“…Thus, the total mass of IMQ distributed daily to each mouse is 3.125 mg. This dose has been empirically determined [ 4 ] and already demonstrated to cause reproducible and optimal skin inflammation in this model in various publications [ 7 , 27 , 31 , 32 , 33 ]. The control group was treated similarly with Lanette cream containing cetyl stearyl alcohol (BASF, Ludwigshafen, Germany).…”