Elevated Expression of NLRP1 and IPAF Are Related to Oral Pemphigus Vulgaris Pathogenesis

Abstract

Oral pemphigus vulgaris (PV) is a rare blistering disorder of the skin and mucous membranes in the mouth. Inflammasome serves as a molecular platform that mediates the autoactivation of caspase-1, which cleaves the pro-forms of IL-1β and IL-18 to active forms. Therefore, the main aim of this study was to evaluate the messenger RNA (mRNA) levels of NOD-like receptor-related protein (NLRP)1, NLRP3, and IPAF in the PBMCs of PV patients to determine their effect in PV pathogenesis. This study was designed as a cross-sectional study. We studied mRNA levels of three types of inflammasomes including NLRP1, NLRP3, and IPAF in 43 oral PV patients and 40 healthy controls by real-time PCR technique. Results were analyzed by SPSS software package version 18. Here, we showed that the mRNA levels of NLRP1 and IPAF in patients with active PV remarkably increased compared to those in healthy controls. However, the mRNA level of NLRP3 in PBMC of PV patients was similar to that of the control group. We showed important and emerging relationship of NLRP1 and IPAF mRNAs with PV disease progression. We hypothesize that NLRP1 and IPAF with cytokine activity of IL-1β are involved in the inflammation in PV patients.

Elevated caspase-1 activity and IL-1β expression are associated with the IPAF inflammasome in an experimental model of allergy

“…In addition, caspase-1 activation may lead to the processing and maturation of IL-1β, thus resulting in allergic symptoms in the sensitized mice. In accordance with these results, a previous study reported that elevated expression of IPAF, alongside IL-1β, is involved in the inflammation of patients with pemphigus vulgaris (33). In addition, Liu and Chan (34) revealed that palmitate was able to induce the production of IL-1β via activation of the IPAF-ASC inflammasome in primary astrocytes.…”

Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation

“…Similar to caspase-5, associated NLRP1 was also suppressed, IL-1β-levels reduced (0.6-fold, p = 0.16), whereas caspase-1 levels remained unaffected (Fig 5H, data not shown). Together, data suggest that targeting caspase-5 may contribute to the anti-inflammatory effects of vitamin D that could be relevant for treatment of Th17-mediated autoinflammatory diseases with caspase-5 overexpression, such as psoriasis or lupus erythematosus (S4 Fig, S5 Fig), or others with proposed NLRP1 inflammasome activity[20, 21]. …”

“…Increasing evidence connects the NLRP1 inflammasome to the pathogenesis of skin-associated autoimmune diseases, such as vitiligo, lupus erythematosus, pemphigus vulgaris, and psoriasis [15, 17, 20, 45]. Compared to other inflammasome complexes, such as NLPR3 and AIM2 expressed in keratinocytes, NLRP1 can activate caspase-5 besides inflammasome ubiquitous caspase-1 [8, 11].…”

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

“…Also, several studies have demonstrated the differences between sera cytokines levels of pemphigus patients and healthy controls (systematically reviewed by Tavakolpour et al 9 ), while there are limited reports regarding different genes' expression profile in comparison with healthy controls. The expression of NLRP1 , 10 IPAF , 10 CD19 genes, 11 and some miRNAs including miR‐424‐5p 12 and miRNA‐338‐3p 13 were demonstrated to be significantly increased in blood samples of PV and/or PF patients. Moreover, overexpression of IL17 and IL23 genes were reported to be occurred in lesion biopsy samples of pemphigus patients 14 .…”