title: Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling.
abstract: Heme oxygenase-1 (HO-1), a stress-inducible protein with a potential anti-inflammatory effect, plays an important role in skin injury and wound healing. However, the function of HO-1 in cutaneous inflammatory diseases, such as psoriasis, remains unknown. The abnormal activation of Stat3, a known transcription factor that induces inflammation and regulates cell differentiation, is directly involved in the pathogenesis and development of psoriasis. Hence, targeting Stat3 is potentially beneficial in the treatment of psoriasis. In this study, HO-1 activation significantly alleviated the disease-related pathogenesis abnormality. To determine the mechanism by which HO-1 exerts immune protection on Th17-related cytokines, IL6/IL22-induced Stat3 activation was significantly suppressed, accompanied by decreased cell proliferation and reversed abnormal cell proliferation. Importantly, HO-1-induced Stat3 suppression was mediated through the activation of protein tyrosine phosphatase SHP-1. Overall, our study provides direct evidence indicating that HO-1 might be a useful therapeutic target for psoriasis. SHP-1-mediated suppression of Stat3 activation after HO-1 activation is a unique molecular mechanism for the regulation of Stat3 activation.
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.|Central Laboratory, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, Jiangsu, 210029, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.|Nanjing Stomatology Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210093, China.
authors.forename: Sijing
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Zhonglan
authors.initials: Z
authors.lastname: Su
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Song
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Esthetic Plastic Surgery, The First Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Wangsen
authors.initials: W
authors.lastname: Cao
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Yin
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D000077271:Imiquimod; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D050796:STAT3 Transcription Factor; D051547:Heme Oxygenase-1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D000077271:Imiquimod