Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients

Maria A. Martínez-Godínez, Maria del Pilar Cruz-Domínguez, Luis J. Jara, Aarón Domínguez-López, Rosa A. Jarillo-Luna, Olga Vera-Lastra, Daniel H. Montes-Cortes, Rafael Campos-Rodríguez, Dulce M. López-Sánchez, Cesar M. Mejía-Barradas, Enrique E. Castelán-Chávez, Angel Miliar-García

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotidebinding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL- 1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Original languageEnglish
Pages (from-to)5-10
Number of pages6
JournalIsrael Medical Association Journal
Volume17
Issue number1
StatePublished - 1 Jan 2015

Keywords

  • Caspase-1
  • Inflammasome
  • NLRP3
  • Skin
  • Systemic sclerosis (SSc)

Fingerprint

Dive into the research topics of 'Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients'. Together they form a unique fingerprint.

Cite this