title: 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.
authors.affiliation: Department of Dermatovenereology, Chengdu Second People's Hospital, Chengdu, China.|Department of Dermatovenereology, West China Hospital of Sichuan University, Chengdu, China.|Department of Dermatovenereology, Chengdu Qingbaijiang Distinct People's Hospital, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Dermatovenereology, Chengdu Second People's Hospital, Chengdu, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Fu
authors.affiliation: Department of Dermatovenereology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Zai-Pei
authors.initials: ZP
authors.lastname: Guo
authors.affiliation: Department of Dermatovenereology, Chengdu Second People's Hospital, Chengdu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Dermatovenereology, Chengdu Second People's Hospital, Chengdu, China.
authors.forename: Na
authors.initials: N
authors.lastname: Cao
authors.affiliation: Department of Dermatovenereology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Qin
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000378:metabolism*; D000077271:Imiquimod; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D010936:Plant Extracts; D019695:Glycyrrhizic Acid; D000077271:Imiquimod
keywords: glycyrrhizin; high mobility group box-1; imiquimod; inflammation; psoriasis