TY - JOUR
T1 - Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients
AU - Martínez-Godínez, Maria A.
AU - Cruz-Domínguez, Maria del Pilar
AU - Jara, Luis J.
AU - Domínguez-López, Aarón
AU - Jarillo-Luna, Rosa A.
AU - Vera-Lastra, Olga
AU - Montes-Cortes, Daniel H.
AU - Campos-Rodríguez, Rafael
AU - López-Sánchez, Dulce M.
AU - Mejía-Barradas, Cesar M.
AU - Castelán-Chávez, Enrique E.
AU - Miliar-García, Angel
N1 - Publisher Copyright:
© 2015 Israel Medical Association. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Caspase-1
KW - Inflammasome
KW - NLRP3
KW - Skin
KW - Systemic sclerosis (SSc)
UR - http://www.scopus.com/inward/record.url?scp=84921866275&partnerID=8YFLogxK
M3 - Artículo
SN - 1565-1088
VL - 17
SP - 5
EP - 10
JO - Israel Medical Association Journal
JF - Israel Medical Association Journal
IS - 1
ER -