title: Proinflammatory effect of high-mobility group protein B1 on keratinocytes: an autocrine mechanism underlying psoriasis development.
abstract: Psoriasis is an autoimmune skin disease, in which keratinocytes play a crucial pathogenic role. High-mobility group protein B1 (HMGB1) is an inflammatory factor that can be released from keratinocyte nuclei in psoriatic lesions. We aimed to investigate the proinflammatory effect of HMGB1 on keratinocytes and the contribution of HMGB1 to psoriasis development. Normal human keratinocytes were treated with recombinant human HMGB1, and the production of inflammatory factors and the intermediary signalling pathways were examined. Furthermore, the imiquimod-induced psoriasis-like mouse model was used to investigate the role of HMGB1 in psoriasis development in vivo. A total of 11 inflammatory factors were shown to be upregulated by HMGB1 in keratinocytes, among which interleukin (IL)-18 showed the greatest change. We then found that activation of the nuclear factor-κB signalling pathway and inflammasomes accounted for HMGB1-induced IL-18 expression and secretion. Moreover, HMGB1 and downstream IL-18 contributed to the development of psoriasiform dermatitis in the imiquimod-treated mice. In addition, T-helper 17 immune response in the psoriasis-like mouse model could be inhibited by both HMGB1 and IL-18 blockade. Our findings indicate that HMGB1 secreted from keratinocytes can facilitate the production and secretion of inflammatory factors such as IL-18 in keratinocytes in an autocrine way, thus promoting the development of psoriasis. Blocking the proinflammatory function of the HMGB1-IL-18 axis may be useful for psoriasis treatment in the future. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Huina
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, PR China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
mesh_terms: D000634:Aminoquinolines / Q000627:therapeutic use; D000818:Animals; D019898:Autocrine Communication; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D000077271:Imiquimod; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology; D020382:Interleukin-18 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C582808:HMGB1 protein, mouse; D058847:Inflammasomes; D020381:Interleukin-17; D020382:Interleukin-18; D000077271:Imiquimod
keywords: HMGB1; IL-18; NF-κB; imiquimod; inflammasome; keratinocyte; psoriasis