title: Proteolytic activity and expression of the 20S proteasome are increased in psoriasis lesional skin.
abstract: BACKGROUND
  Deregulation of the proteasome pathway has been shown to be involved in the pathogenesis of several inflammatory disorders. To date limited information exists on proteasome and immunoproteasome expression and activity in psoriasis skin.
  
  
  OBJECTIVE
  To investigate the potential role of proteasomes in the pathogenesis of psoriasis.
  
  
  METHODS
  Thirty-six patients with psoriasis and 40 healthy subjects were included. The protein and mRNA expression levels and proteolytic activity of proteasome and immunoproteasome subunits were determined using immunohistochemistry, quantitative polymerase chain reaction and fluorogenic peptide substrate in lesional and nonlesional psoriasis skin. We additionally measured the plasmatic proteasome (p-proteasome) levels using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We reveal an increased expression of proteasome and immunoproteasome subunits but stable mRNA levels in lesional psoriasis skin as compared with nonlesional psoriasis skin (n = 19), suggesting that proteasome and immunoproteasome expression is regulated post-transcriptionally. This proteasome overexpression was associated with a significant increase of the proteasomal chymotrypsin-like activity that was threefold higher in lesional skin than in nonlesional skin (n = 3). p-Proteasome levels were enhanced in patients with psoriasis (mean ± SEM 3960 ± 299 ng mL(-1) , range 1484-8987) when compared with controls (2535±187 ng mL(-1) , range 654-6446, P<0·001) and were significantly higher in psoriatic arthritis (4937±572 ng mL(-1) , range 2600-8987). In addition, they were correlated to the body surface area involved and appeared thus as a new biomarker of psoriasis severity.
  
  
  CONCLUSIONS
  Altogether these results strongly suggest the involvement of the proteasome system in the pathogenesis of psoriasis and support the relevance of proteasome inhibitors in local or systemic treatment of psoriasis.
authors: Laboratoire d'Histologie-Embryologie-Cytogénétique, Université Montpellier 1, Faculté de Médecine Montpellier-Nîmes, Nîmes, France.
authors: L
authors: L
authors: Henry
authors: L
authors: L
authors: Le Gallic
authors: G
authors: G
authors: Garcin
authors: O
authors: O
authors: Coux
authors: N
authors: N
authors: Jumez
authors: P
authors: P
authors: Roger
authors: T
authors: T
authors: Lavabre-Bertrand
authors: J
authors: J
authors: Martinez
authors: L
authors: L
authors: Meunier
authors: P E
authors: PE
authors: Stoebner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015535:Arthritis, Psoriatic / Q000201:enzymology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011565:Psoriasis / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex