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.

Increased Expression and Activation of Absent in Melanoma 2 Inflammasome Components in Lymphocytic Infiltrates of Abdominal Aortic Aneurysms

“…The latter has little IL-1β procession activity, is induced by lipopolysaccharide (LPS) and interferon γ (IFN-γ) and appears to cooperate with other inflammatory caspases for full activity (26). Recently, caspase-5 has been found to be upregulated in lesional psoriatic skin (27) and was shown to be involved in inflammatory responses of human retinal pigment epithelial cells (28), which supports a specific role of caspase-5 in sterile chronic inflammation. In line with these findings, we here detected significantly increased amounts of mature, active caspase-5 (p20) in the aortic wall of AAA samples compared with normal aorta.…”

Psoriasis as Autoinflammatory Disease

“…57 An important signal activating inflammasome-mediated inflammation is cytosolic DNA. 58 The cytosolic DNA acts as a signal capable of activating inflammasomes via the DNA sensor AIM2.…”

Psoriasis Treatment Changes the Expression Profile of Selected Caspases and their Regulatory MicroRNAs

“…For instance, in psoriatic lesions there occurs overexpression of caspase-5 [23] and irregular activity of caspase-1 is observed in the course of many other pro-inflammatory diseases [10].…”