title: Caspase-5 expression is upregulated in lesional psoriatic skin.
abstract: The inflammasome is a cytosolic multiprotein complex with two major functions: recognizing pathogen-associated molecular patterns and reacting to these through activation of the proinflammatory cytokines IL-1β and IL-18. In this study, we characterized the expression of inflammasome components in psoriatic skin and other common inflammatory skin diseases. Human skin biopsy specimens, cultured primary human keratinocytes, and peripheral blood mononuclear cells (PBMCs) were analyzed using quantitative reverse transcriptase-PCR (RT-PCR) and semiquantitative western blotting. mRNA expression of the inflammasome components NALP1, NALP3, ASC, caspase-1, caspase-4, and caspase-5 was detected in psoriatic skin. Interestingly, we found an extensive, 20-fold upregulation (P<0.01) of caspase-5 mRNA in lesional compared with nonlesional psoriatic skin, whereas caspase-1, caspase-4, and ASC (apoptosis-associated speck-like protein with CARD domain) mRNAs were upregulated by only 1.5- to 2.6-fold (P<0.01). Caspase-5 mRNA was not increased in biopsies from other inflammatory skin diseases, suggesting that this finding could be psoriasis specific. In vitro experiments revealed that caspase-5 mRNA was induced in primary keratinocytes as well as PBMCs stimulated with IFN-γ. Inhibition studies suggested that caspase-5 mRNA upregulation was mediated through the NF-κB pathway. Our findings suggest that caspase-5 and the inflammasome may have an important role in the inflammatory response in psoriasis.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Salskov-Iversen
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.forename: Knud
authors.initials: K
authors.lastname: Kragballe
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001706:Biopsy; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D007371:Interferon-gamma; C099217:CASP5 protein, human; D020169:Caspases