Caspase-5 Expression Is Upregulated in Lesional Psoriatic Skin

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Caspase-5 Expression Is Upregulated in Lesional Psoriatic Skin Maria L. Salskov-Iversen, Claus Johansen, Knud Kragballe, Lars Iversen Journal of Investigative Dermatology Volume 131, Issue 3, Pages 670-676 (March 2011) DOI: 10.1038/jid.2010.370 Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Expression of inflammasome-associated components in plaque psoriasis. (a) mRNA expression, relative to housekeeping gene RPLP0, was analyzed by reverse transcriptase–PCR (RT-PCR). Bars indicate mean mRNA levels±SD in paired samples from nonlesional psoriatic skin (index 100) and plaque lesions (n=9). **P<0.01. Protein extract from paired keratome biopsies from nonlesional and lesional psoriatic skin was analyzed by western blotting. (b) Caspase-5 and β-actin blots from five psoriatic patients. (c) Relative expression of caspase-5 protein±SD; n=5. **P<0.01. Journal of Investigative Dermatology 2011 131, 670-676DOI: (10.1038/jid.2010.370) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Relative caspase-5 mRNA expression during different phases of psoriasis and in other inflammatory skin diseases. Caspase-5 mRNA expression, relative to the housekeeping gene RPLP0, was analyzed by reverse transcriptase–PCR (RT-PCR). Bars indicate the mean caspase-5 mRNA expression±SD. (a) Three biopsy samples were donated by each of the psoriatic patients presenting both guttate and plaque elements (n=6). Nonlesional skin was indexed at 100. The first bar represents the mean caspase-5 mRNA expression in normal skin (n=3). *P<0.05, **P<0.01. (b) Caspase-5 mRNA expression in other inflammatory skin diseases. Normal skin was indexed at 100 (n=3). Bars labeled with “-” or “+” indicate the mean caspase-5 mRNA expression in uninvolved/involved skin from patients with atopic dermatitis (n=6) or nickel-induced acute contact dermatitis (n=5). Journal of Investigative Dermatology 2011 131, 670-676DOI: (10.1038/jid.2010.370) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Relative caspase-5 mRNA expression decreases with clinical resolution during anti-tumor necrosis factor-α (TNF-α) treatment. (a) Caspase-5 mRNA expression, relative to the housekeeping gene RPLP0, was analyzed by reverse transcriptase–PCR (RT-PCR). Punch biopsies were taken on days 0, 4, and 14 after treatment initiation. Bars indicate mean caspase-5 mRNA expressions±SD; n=5, *P<0.05. (b) The Psoriasis Area and Severity Index (PASI) scores of the same five patients (pt.) as in a during anti-TNF-α treatment. Journal of Investigative Dermatology 2011 131, 670-676DOI: (10.1038/jid.2010.370) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Induction of caspase-5 mRNA in keratinocytes and peripheral blood mononuclear cells (PBMCs) in vitro. Caspase-5 mRNA expression, relative to the housekeeping gene RPLP0, was analyzed by reverse transcriptase–PCR (RT-PCR). (a) Results from cultured normal human keratinocytes (n=4–6). (b) Normal human PBMCs (n=5 to 6) in vitro. Tumor necrosis factor-α (TNF-α; 10μgml–1), IL-17A (200ngml–1), a combination of TNF-α and IL-17A, IL-22 (100ngml–1), a combination of TNF-α and IL-22, or lipopolysaccharide (LPS; 100ngml–1). Vehicle-treated controls were indexed at 100. *P<0.05. Journal of Investigative Dermatology 2011 131, 670-676DOI: (10.1038/jid.2010.370) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Caspase-5 mRNA is induced through the NF-κB signaling pathway. Cultured normal human peripheral blood mononuclear cells (PBMCs) were preincubated with either the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190 (10μM), or an inhibitor of the NF-κB pathway, IKK2 (50μM), 45minutes before overnight stimulation with lipopolysaccharide (LPS). Caspase-5 mRNA expression, relative to RPLP0, was analyzed by reverse transcriptase–PCR (RT-PCR); n=6, *P<0.05. Journal of Investigative Dermatology 2011 131, 670-676DOI: (10.1038/jid.2010.370) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions