title: Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice.
abstract: OBJECTIVE
  The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ.
  
  
  RESULTS
  Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as toll-like receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation.
  
  
  CONCLUSIONS
  Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression.
authors.affiliation: 1 Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Shyam Kishor
authors.initials: SK
authors.lastname: Sah
authors.affiliation: 2 Biological Sciences Center, University of Minnesota Twin Cities , St. Paul, Minnesota.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: 3 Department of Bioengineering, College of Engineering, Hanyang University , Seoul, Republic of Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: 4 Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University , Seoul, Republic of Korea.
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.affiliation: 1 Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea.
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D000077271:Imiquimod; D018836:Inflammation Mediators / Q000378:metabolism; D053612:Janus Kinases; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009081:Mucolipidoses; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D011565:Psoriasis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050791:STAT Transcription Factors; D051199:Toll-Like Receptor 7; D013482:Superoxide Dismutase; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases; D000077271:Imiquimod