Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients.
| Autor: | Martínez-Godínez MA, Cruz-Domínguez MP, Jara LJ, Domínguez-López A, Jarillo-Luna RA, Vera-Lastra O, Montes-Cortes DH, Campos-Rodríguez R, López-Sánchez DM, Mejía-Barradas CM, Castelán-Chávez EE, Miliar-García A |
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| Jazyk: | angličtina |
| Zdroj: | The Israel Medical Association journal : IMAJ [Isr Med Assoc J] 2015 Jan; Vol. 17 (1), pp. 5-10. |
| Abstrakt: | 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 (nucleotide-binding 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. |
| Databáze: | MEDLINE |
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