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

In the previous work, we have indicated that HMGB 1, a pro‐inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB 1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB 1 application and HMGB 1 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 HMGB 1 or phosphate‐buffered saline ( PBS ) i.d. Abundant cytoplasmic expression of HMGB 1 was observed in lesional skin from IMQ ‐treated skin. The injection of HMGB 1 into the IMQ ‐treated skin further aggravated the psoriasis‐like disease, enhanced the infiltration of CD 3 + T cells, myeloperoxidase + neutrophils and CD 11c + 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‐ HMGB 1 monoclonal antibody or HMGB 1 inhibitor glycyrrhizin, we indicated that HMGB 1 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 HMGB 1 may act as a pro‐inflammatory cytokine, and contribute to the development of IMQ ‐induced psoriasis‐like inflammation. HMGB 1 blockade may represent a new direction in the suppression of psoriasis.