The activation of NLRP3 inflammasome in the dermal fibroblasts of systemic sclerosis

Karabay U., Yüce İnel T., Yüksel Eğrilmez M., Öztürk F. A., Vayvada H., Birlik A. M.

47th FEBS Congress, Tours, Fransa, 8 - 12 Temmuz 2023, cilt.13, ss.245-246

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 13
  • Basıldığı Şehir: Tours
  • Basıldığı Ülke: Fransa
  • Sayfa Sayıları: ss.245-246
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized

by progressive fibrosis. The precise mechanisms of SSc

remain poorly understood. NLRP3 inflammasome is a key player

in regulating host immune responses to infection. NLRP3 inflammasome

activation is associated with autoimmune rheumatic diseases.

Once NLRP3 is activated, NLRP3 interacts with NEK7,

then recruits ASC and caspase-1 assembling into NLRP3 inflammasome,

which leads to maturation and excretion of proinflammatory

cytokines IL-1b and IL-18. The link between NLRP3

inflammasome activation and SSc pathogenesis has recently been

established. The aim of this study is to investigate gene expression

levels of NEK7, caspase-1, IL-1b, IL-18, and type I collagen

a1 chain (COL1A1) in the dermal fibroblasts of SSc patients.

Nine patients with SSc and 3 healthy controls were enrolled in

the study after they signed a written informed consent form. We

obtained punch biopsy samples of the affected skin over the dorsal

mid-forearm from each individual. Dermal fibroblasts were

prepared from skin samples of SSc patients and healthy controls.

Total RNA was isolated from cells and cDNA synthesis was performed.

The mRNA expression levels of NEK7, IL-1b, IL-18,

caspase-1 and COL1A1 were measured by qPCR. Quantification

of gene expression was calculated using the DDCt method. Our

results showed that mRNA levels of IL-1b and IL-18 were significantly

increased in the dermal fibroblasts of SSc patients compared

with healthy controls. COL1A1 mRNA level was also

significantly increased in SSc patients compared with healthy

controls showing skin fibrosis in patients. Although NEK7 and

caspase-1 mRNA levels were higher in dermal fibroblasts of SSc

patients compared with controls, no significant difference was

found between groups. Our results demonstrate that IL-1b, IL-18 and COL1A1 mRNA levels were increased in the dermal fibroblasts

of SSc patients suggesting the important role of NLRP3

inflammasome activation in the pathogenesis of SSc.