Hyperexpression of NLRP1 inflammasome complex and cytokines IL-1β, IL-18 genes in bioptates of lesion and healhy skin of patients with psoriasis

• Ekaterina D. Merkushova
• Elena M. Khasanova
• Lyudmila V. Gankovskaya

Abstract

Introduction. Psoriasis (PS) is a chronic multifactorial auto-inflammatory skin disease characterized by hyperproliferation of epidermal cells and impaired differentiation of keratinocytes. In recent years more attention has been paid to the role of innate immunity in the pathogenesis of psoriasis and its genetic regulation.

Aim - to study the expression of genes of innate immunity receptors TLR7, TLR9, components of the NLRP1, NLRP3, ASC, CASP1, CASP5 and genes of interleukin(IL)-1β and IL-18.

Material and methods. Totally 32 participants were included in the study. The main group consisted of 21 patients with severe and moderate psoriasis. Patients in the main group underwent a biopsy of healthy and psoriatic skin. 11 healthy donors formed the comparison group. RNA was isolated from the obtained skin biopsies and gene expression was determined by real-time PCR. The expression of target genes was normalized to the housekeeping gene coding β-actin.

Results. It was shown a statistically significant increase in the expression of innate immunity genes in keratinocytes of patients with psoriasis. The expression of TLR9 was higher in both the psoriatic and unaffected skin by 4.8 and 4.3 times, respectively, compared to the control group. At the same time, overexpression of the NLRP1 was detected: 5 times more in affected skin and 3.4 times more in unaffected skin in comparison with healthy donors. CASP5 is a component of the NLRP1 inflammasome complex which provides pro-IL1 and pro-IL-18 processing. Our study showed a significant increase in the expression of the CASP5 gene in the cells of the affected and unaffected skin vs group of comparison by 200 and 194 times, respectively. Activation of CASP5 provides maturation of the active forms of pro-IL1p and pro-IL 18 which increased expression was also revealed in the work.

Discussion. An increase in the expression of TLR7 and TLR9 genes in skin cells of psoriatic patients confirms the significance of the role of these receptors in the pathogenesis of psoriasis. The main function of TLR7 and TLR9 is recognizing endogenous danger signals, in particular auto-RNA and auto-DNA, which are actively released from destroyed keratinocytes in psoriatic inflammation. Activation of TLR7 and TLR9 can stimulate increased expression of the NLRP1 and NLRP3 inflammasome complexes. The revealed predominant overexpression of NLRP1 inflammasome genes indicates that it may play a greater role in the development of psoriasis than the NLRP3 complex. After NLRP1 activation it binds the CASP1 and CASP5 molecules, which genes’ significantly increased expression was demonstrated. At the same time, it is necessary to note the increase of the expression of target genes in both healthy and affected skin of patients with psoriasis, which indicates a systematic change of the innate immunity in the psoriatic process.

Conclusion. The obtained data can be used for a more detailed study of specific signaling pathways of activation of inflammasome complexes and cytokines participation in the development of the psoriatic process and also become the basis for early diagnosis of psoriasis.

Keywords:innate immunity; psoriasis; inflammasoma; Toll-like receptors; inflammation; targeted therapy

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