title: Increased Lipocalin-2 Contributes to the Pathogenesis of Psoriasis by Modulating Neutrophil Chemotaxis and Cytokine Secretion.
abstract: Psoriasis is characterized by resistance to infections, which is regulated by antimicrobial proteins. Whether antimicrobial proteins play a pathogenic role in psoriasis remains unclear. In this study, we aimed to elucidate the role of lipocalin-2 (Lcn2), an antimicrobial protein, in the pathogenesis of psoriasis. Our results showed that Lcn2 was highly expressed in the lesional skin of psoriatic patients. The neutralization of Lcn2 alleviated epidermal hyperplasia, inflammation, and especially neutrophil infiltration in an imiquimod-induced psoriasis-like murine model. In vitro, Lcn2 stimulated human neutrophils to produce vital proinflammatory mediators, such as IL-6, IL-8, tumor necrosis factor-α, and IL-1α via a specific receptor, 24p3R, on neutrophils, which consequently activated the downstream extracellular signal-regulated kinase-1/2 and p38-mitogen-activated protein kinase signaling pathways. Moreover, Lcn2-induced neutrophil chemotaxis was concentration dependent and mediated by the extracellular signal-regulated kinase-1/2 and p38-mitogen-activated protein kinase signaling pathways in vitro. Furthermore, we demonstrated that both keratinocytes and neutrophils were the sources of Lcn2 in the lesional skin of psoriatic patients. Taken together, these results suggest that Lcn2 is involved in the pathogenesis of psoriasis by modulating neutrophil function, and that it could serve as a potential target for treating psoriasis.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjwgang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001706:Biopsy; D002454:Cell Differentiation; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism*; D004817:Epidermis / Q000276:immunology; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation; D000071068:Lipocalin-2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D016207:Cytokines; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000077271:Imiquimod