Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?
Document Type
Article
Publication Date
3-19-2021
Publication Title
Reumatologia Clinica
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.
First Page
187
Last Page
191
PubMed ID
31917141
Volume
17
Issue
4
Publisher
Elsevier
Recommended Citation
Perez-Alamino, Rodolfo; Cuchacovich, Raquel; Espinoza, Luis R.; Porretta, Constance P.; and Zea, Arnold H., "Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?" (2021). School of Graduate Studies Faculty Publications. 36.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/36
10.1016/j.reuma.2019.10.007