title: Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis.
abstract: BACKGROUND
  Psoriasis is a Th1 immune-mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the 'psoriatic march'. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis.
  
  
  OBJECTIVE
  Evaluation of VEGF expression and production, nitric oxide (NO) production, iNOS expression, and the antioxidant response of mesenchymal stem cells (MSCs), both before and after 12 weeks of treatment with the TNF-α inhibitors adalimumab or etanercept.
  
  
  METHODS
  Biochemical, morphological and immunohistochemical analyses were performed in MSCs isolated from nonlesional, perilesional and lesional skin of patients with psoriasis, before and after treatment.
  
  
  RESULTS
  The treatments were able to reduce the expression and production of VEGF, the expression of iNOS and the production of NO in MSCs of patients with psoriasis. TNF-α inhibitors also reduced the oxidative damage in MSC membrane and proteins, several antioxidant systems responded to treatments with a general inhibition of activities (glutathione S-transferase and catalase) and these effects were also supported by a general decrease of total oxyradical scavenging capacity towards hydroxyl radicals and peroxynitrite.
  
  
  CONCLUSIONS
  TNF-α inhibitors are able to change the physiopathological pathway of psoriasis, and our results suggest their therapeutic effects already take place at the level of MSCs, which probably represent the cells primarily involved in the 'psoriatic march'.
authors.affiliation: Dermatological Clinic, Department of Molecular and Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Campanati
authors.forename: M
authors.initials: M
authors.lastname: Orciani
authors.forename: S
authors.initials: S
authors.lastname: Gorbi
authors.forename: F
authors.initials: F
authors.lastname: Regoli
authors.forename: R
authors.initials: R
authors.lastname: Di Primio
authors.forename: A
authors.initials: A
authors.lastname: Offidani
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001691:Biological Therapy / Q000379:methods*; D016022:Case-Control Studies; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000068879:Adalimumab; D000068800:Etanercept