Downregulation of NLRP3, CASP1 and IL1B expression in COPD patients after lung transplantation

Abstract

Introduction: Emerging evidence suggests that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays an important role in the pathogenesis of COPD. Moreover, it may be involved in ongoing chronic inflammation that is present in patients with end-stage COPD who are candidates for lung transplantation (LT). Aims and objectives: The aim of this study was to determine the gene expression of NLRP3, caspase-1 (CASP1) and interleukin-1β (IL1B) in 5 patients with COPD before LT and 1 year after LT.

Methods: Gene expression was examined by qPCR in the peripheral blood samples using the commercial TaqMan gene expression assays and the calculation of the relative mRNA expression was performed by the 2^−∆∆Ct method. Spirometry parameters were determined before and after LT while symptoms burden, history of exacerbations and health status were assessed by mMRC, CAT and SGRQ-C scores. Results were statistically significant if P < 0.05.

Results: Gene expressions of NLRP3, CASP1 and IL1B were significantly downregulated in patients one year after LT (P=0.009, P=0.014, P=0.005, respectively). On the other hand, spirometry values were significantly increased at 1-year post-transplantation period with FEV₁ (L) increasing from 0.59 to 3.22 (P=0.002) and FVC (L) from 1.81 to 3.57 (P=0.014). In addition, significant improvements in mMRC, CAT and SGRQ-C scores were observed after LT (P=0.041, P=0.035 and P= 0.015, respectively).

Conclusions: NLRP3, CASP1 and IL1B expression were decreased in lung transplant recipients with COPD one year after LT, suggesting a significant involvement of NLRP3 inflammasome in severe COPD.