Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome.
Espiridión Ramos-MartinezAngel E Vega-SánchezGloria Pérez-RubioMayra MejiaIvette Buendia-RoldanMontserrat I González-PérezHeidegger N Mateos-ToledoWarrison Athanasio AndradeRamcés Falfan-ValenciaJorge Rojas SerranoPublished in: Cells (2022)
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.
Keyphrases
- interstitial lung disease
- systemic sclerosis
- cell death
- nlrp inflammasome
- end stage renal disease
- newly diagnosed
- ejection fraction
- rheumatoid arthritis
- prognostic factors
- induced apoptosis
- idiopathic pulmonary fibrosis
- immune response
- multiple sclerosis
- oxidative stress
- patient reported outcomes
- dendritic cells
- cell cycle arrest
- cell proliferation
- single cell
- protein protein
- case report
- patient reported
- signaling pathway
- mesenchymal stem cells
- cell therapy
- smooth muscle