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Article

Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome

by
Espiridión Ramos-Martinez
1,†,
Angel E. Vega-Sánchez
2,†,
Gloria Pérez-Rubio
3,
Mayra Mejia
2,
Ivette Buendía-Roldán
4,
Montserrat I. González-Pérez
2,
Heidegger N. Mateos-Toledo
2,
Warrison A. Andrade
5,
Ramcés Falfán-Valencia
3,* and
Jorge Rojas-Serrano
2,*
1
Experimental Medicine Research Unit, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 06720, Mexico
2
Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico
3
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico
4
Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico
5
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2023, 12(1), 60; https://doi.org/10.3390/cells12010060
Submission received: 18 November 2022 / Revised: 17 December 2022 / Accepted: 18 December 2022 / Published: 23 December 2022
(This article belongs to the Special Issue Autoimmune Diseases: Molecular Mechanisms and Therapies)

Abstract

Anti-synthetase syndrome (ASSD) is an autoimmune disorder characterized by inflammatory interstitial lung disease (ILD). The main objective of this work was to quantify the concentrations of cytokines and molecules associated with inflammasome activation in bronchoalveolar lavage (BAL) of patients with ASSD and a comparison group of systemic sclerosis (SSc) patients. Cytokines and lactate dehydrogenase (LDH) were determined using the concentrated BAL protein. The activity of caspase-1 and concentration of NLRP3 with the protein purified from the cell pellet in each group of patients. We found higher caspase-1 levels in ASSD vs. SSc, 1.25 RFU vs. 0.75 RFU p = 0.003, and LDH levels at 0.15 OD vs. 0.09 OD p < 0.001. A significant difference was observed in molecules associated with inflammasome activation, IL-18: 1.42 pg/mL vs. 0.87 pg/mL p = 0.02 and IFN-γ: 0.9 pg/mL vs. 0.86 pg/mL, p = 0.01. A positive correlation was found between caspase-1 and LDH in the patients with ASSD Rho 0.58 (p = 0.008) but not in the SSc group. In patients with ASSD, greater caspase-1 and higher LDH activity were observed in BAL, suggesting cell death due to pyroptosis and activation of the inflammasome pathway.
Keywords: anti-synthetase syndrome; interstitial lung disease; inflammasome; caspase-1; autoantibodies anti-synthetase syndrome; interstitial lung disease; inflammasome; caspase-1; autoantibodies
Graphical Abstract

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MDPI and ACS Style

Ramos-Martinez, E.; Vega-Sánchez, A.E.; Pérez-Rubio, G.; Mejia, M.; Buendía-Roldán, I.; González-Pérez, M.I.; Mateos-Toledo, H.N.; Andrade, W.A.; Falfán-Valencia, R.; Rojas-Serrano, J. Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome. Cells 2023, 12, 60. https://doi.org/10.3390/cells12010060

AMA Style

Ramos-Martinez E, Vega-Sánchez AE, Pérez-Rubio G, Mejia M, Buendía-Roldán I, González-Pérez MI, Mateos-Toledo HN, Andrade WA, Falfán-Valencia R, Rojas-Serrano J. Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome. Cells. 2023; 12(1):60. https://doi.org/10.3390/cells12010060

Chicago/Turabian Style

Ramos-Martinez, Espiridión, Angel E. Vega-Sánchez, Gloria Pérez-Rubio, Mayra Mejia, Ivette Buendía-Roldán, Montserrat I. González-Pérez, Heidegger N. Mateos-Toledo, Warrison A. Andrade, Ramcés Falfán-Valencia, and Jorge Rojas-Serrano. 2023. "Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome" Cells 12, no. 1: 60. https://doi.org/10.3390/cells12010060

APA Style

Ramos-Martinez, E., Vega-Sánchez, A. E., Pérez-Rubio, G., Mejia, M., Buendía-Roldán, I., González-Pérez, M. I., Mateos-Toledo, H. N., Andrade, W. A., Falfán-Valencia, R., & Rojas-Serrano, J. (2023). Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome. Cells, 12(1), 60. https://doi.org/10.3390/cells12010060

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