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Vol. 17. Issue 4.
Pages 187-191 (April 2021)
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Vol. 17. Issue 4.
Pages 187-191 (April 2021)
Brief Report
DOI: 10.1016/j.reumae.2019.10.004
Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?
Rol de la activación del inflammasome en lupus eritematoso sistémico: están las células del sistema inmune innato activados?
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Rodolfo Perez-Alaminoa,b,
Corresponding author
ofo_pa@hotmail.com

Corresponding author.
, Raquel Cuchacovicha, Luis R. Espinozaa, Constance P. Porrettac, Arnold H. Zead
a Section of Rheumatology, Department of Internal Medicine, LSU Health Sciences Center, 1542 Tulane Avenue, New Orleans, LA 70112, USA
b Section of Rheumatology, Hospital de Clínicas Nicolás Avellaneda, Tucumán, Argentina, 2000 Catamarca Street, Tucumán, PC 4000, Argentina
c School of Medicine, Comprehensive Alcohol Research Center, 533 Bolivar Street, CSRB304, New Orleans, LA 70112, USA
d Stanley S. Scott Cancer Center, Microbiology, Immunology and Parasitology, LSU Health Sciences Center, 533 Bolivar Street, CSRB 305, New Orleans, LA 70112, USA
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Abstract
Background

Systemic lupus erythematosus (SLE) is characterized by a wide spectrum of clinical and immunological abnormalities. New data have emerged about the role of inflammasomes in autoimmune diseases. We aimed to investigate whether basal inflammasome activation occurs in SLE patients, and whether a relationship between inflammasome-related-cytokines and disease activity exists.

Methods

Fourteen (14) consecutive SLE patients and 13 healthy individuals, matched by sex, age and ethnicity, were included. Demographics, laboratory and clinical data were recorded. Peripheral blood mononuclear cells (PBMCs) from patients and controls were obtained and monocytes were isolated by negative selection. Purified monocytes were stimulated with LPS in the presence or absence of Caspase-1 inhibitor. CD14 and Caspase-1 expression were analyzed by flow cytometry. Cytokine levels were determined in plasma and culture supernatants by ELISA. Student's t test and Mann–Whitney tests were used for statistical analysis.

Results

The percentage of CD14+/Caspase-1+ was significantly higher in monocytes from SLE patients compared to normal controls (p<0.01). These findings paralleled with higher plasma levels of IL-1β (p<0.05) and IL-18 (p<0.01) in those patients. Purified monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation where Caspase-1, IL-1β and IL-18 were highly expressed. Plasma levels of IL-18 were also significantly higher in SLE patients with active disease (p<0.05). In addition, the production of IL-18 was reduced by 3 fold when Caspase-1 inhibitor was added to the cultures.

Conclusions

Monocytes from SLE patients exhibited increased inflammasome activation, characterized by high expression of Caspase-1, IL-1β and IL-18. Caspase-1 specific inhibitor decreased inflammasome activation (in vitro) by suppressing the production of IL-18.

Keywords:
Systemic lupus erythematosus
Pathogenesis
Inflammasomes
Innate immunity
Caspase-1
Cytokines
Resumen
Introducción

El lupus eritematoso sistémico (LES) se caracteriza por presentar diversas anormalidades clínicas e inmunológicas. El ensamblaje de los componentes del inflamasoma da lugar a la activación de caspasa-1, generando la liberación de citoquinas pro-inflamatorias IL-1β e IL-18.

Objetivos

Evaluar si existe una activación basal del inflamasoma en pacientes con LES y determinar la asociación de las citoquinas IL-1β e IL-18 con la actividad de la enfermedad.

Materiales y métodos

Se incluyeron 14 (n=14) pacientes consecutivos con LES y 13 (n=13) controles, pareados por edad, sexo y raza. Se recogieron datos clínicos, demográficos y de laboratorio. Los monocitos fueron aislados a partir de células mononucleares de sangre periférica obtenidas de pacientes y controles. Los monocitos purificados fueron estimulados con LPS, en presencia y ausencia de inhibidor de caspasa-1. La expresión de CD14 y caspasa-1 fueron determinados por citometría de flujo. Niveles de citoquinas fueron determinadas en plasma y en sobrenadantes de cultivos mediante técnica de ELISA. Test de Student y Mann-Whitney fueron usados para el análisis estadístico.

Resultados

El porcentaje de CD14+/caspasa-1+ fue significativamente superior en monocitos de pacientes con LES vs. controles (p<0,01). En forma paralela, se encontraron niveles plasmáticos significativamente superiores de IL-1β (p<0,05) y de IL-18 (p<0,01) en pacientes con LES. Monocitos purificados de pacientes lúpicos presentaron una robusta respuesta inflamatoria luego de ser estimulados con LPS, donde caspasa-1, IL-1β e IL-18 fueron altamente expresados. Niveles plasmáticos de IL-18 fueron significativamente mayores en pacientes con LES y enfermedad activa (p<0,05). Por otro lado, la producción de IL-18 se redujo casi 3 veces cuando se agregó inhibidor de caspasa-1 en cultivos.

Conclusiones

Monocitos de pacientes con LES presentaron evidencia de activación de componentes del inflamasoma, caracterizada por una mayor expresión de caspasa-1, IL-1β e IL-18. El inhibidor específico de caspasa-1 disminuyó la activación del inflamasoma in vitro, reduciendo la producción de IL-18.

Palabras clave:
Lupus eritematoso sistémico
Patogénesis
Inflamasoma
Inmunidad innata
Caspasa-1
Citoquinas

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