title: Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin.
abstract: BACKGROUND
  Mammalian target of rapamycin (mTOR) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered mTOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether mTOR signalling also plays a role in the pathogenesis of psoriasis.
  
  
  OBJECTIVE
  To investigate the activation status of mTOR signalling components in psoriasis.
  
  
  METHODS
  Biopsies from lesional and nonlesional skin of patients with psoriasis (n = 10), as well as samples from healthy donors (n = 3), were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated mTOR, phospho-S6 kinase and phospho-S6 ribosomal protein.
  
  
  RESULTS
  We found mTOR and its downstream signalling molecule, the ribosomal protein S6, to be activated in lesional psoriatic skin. While mTOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S6 is active in suprabasal layers of differentiating keratinocytes.
  
  
  CONCLUSIONS
  Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.
authors: Department of Dermatology, Clinic of the Goethe University, Frankfurt am Main, Germany. claudia.buerger@kgu.de
authors: C
authors: C
authors: Buerger
authors: B
authors: B
authors: Malisiewicz
authors: A
authors: A
authors: Eiser
authors: K
authors: K
authors: Hardt
authors: W H
authors: WH
authors: Boehncke
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D010766:Phosphorylation; D011565:Psoriasis / Q000209:etiology / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D038601:Ribosomal Protein S6; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases