Differential expression of NEK7-NLRP3 inflammasome-related genes in systemic sclerosis dermal fibroblasts: a
Tuba Yuce Inel1, Ufkay Karabay2, Mehtap Yuksel Egrilmez2
1Department of Rheumatology, Izmir City Hospital, Izmir, Turkey.
Purpose:
This study investigated the expression of NEK7-NLRP3 inflammasome-related genes in dermal fibroblasts from patients with systemic sclerosis (SSc), focusing on limited (lSSc) and diffuse cutaneous (dSSc) subtypes and their association with skin fibrosis.
Methods:
Dermal fibroblasts were obtained from patients with SSc and age-matched healthy controls. Messenger RNA expression of NEK7, NLRP3, ASC, caspase-1, IL-1β, IL-18, and COL1A1 was measured by real-time polymerase chain reaction.
Results:
The cohort comprised 13 patients with SSc (mean age 53.8 ± 11.7 years, 69.2% female, 53.8% dSSc) and healthy controls. Modified Rodnan skin score (mRSS) and Medsger severity scores were significantly higher in dSSc than in lSSc (p < 0.05), and were strongly correlated (r = 0.893, p < 0.001). Overall expression of inflammasome-related genes did not differ significantly between the total SSc group and controls. However, subgroup analysis revealed a distinct molecular profile. NEK7 and IL-1β expression levels were significantly higher in lSSc fibroblasts than in dSSc fibroblasts (p = 0.01 and p = 0.015, respectively), while NLRP3 expression was increased in lSSc compared with controls (p = 0.01). Within the lSSc subgroup, IL-18 levels were inversely correlated with mRSS (r = -0.883, p = 0.020), and caspase-1 expression was negatively correlated with age (r = -0.928, p = 0.008).
Conclusion:
These findings identify a subtype-specific pattern of inflammasome-related gene expression in SSc dermal fibroblasts and suggest a potential association with the fibrotic phenotype. Further protein-level and functional studies are warranted.