The protective effect of doxofylline against lipopolysaccharides (LPS)-induced activation of NLRP3 inflammasome is mediated by SIRT1 in human pulmonary bronchial epithelial cells

Jiao, Peng; Li, Weiming; Shen, Lin; Li, Yan; Yu, Lili; Liu, Zhaohui

doi:10.1080/21691401.2020.1730391

Cited by 15 publications

(15 citation statements)

References 20 publications

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“…In this study, it was found that the SIRT1 improved these disorders by inhibiting the NLRP3 inflammasome [36]. Another study found that the Doxofylline inhibited NLRP3 inflammasome via SIRT1 and thus prevented inflammation in lung epithelial cells [37]. Studies have shown that the GD15 is able to prevent acute pulmonary inflammation by increasing the expression of SIRT1 in the inflammation-caused lung injury of rats following the NLRP3 inflammasome activation [38].…”

Section: Effect Of Quercetin On Sirt1 As Anti-inflammatory Factor and Nlrp3 Inflammasome Inhibitormentioning

confidence: 71%

Anti-inflammatory potential of Quercetin in COVID-19 treatment

2021

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SARS-CoV-2 is a betacoronavirus causing severe inflammatory pneumonia, so that excessive inflammation is considered a risk factor for the disease. According to reports, cytokine storm is strongly responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Phylogenetic findings show more similarity of the SARS-CoV-2 virus with bat coronaviruses, and less with SARS-CoV. Quercetin is a carbohydrate-free flavonoid that is the most abundant flavonoid in vegetables and fruits and has been the most studied to determine the biological effects of flavonoids. Inflammasomes are cytosolic multi-protein complexes assembling in response to cytosolic PAMP and DAMPs, whose function is to generate active forms of cytokines IL-1β and IL-18. Activation or inhibition of the NLRP3 inflammasome is affected by regulators such as TXNIP, SIRT1 and NRF2. Quercetin suppresses the NLRP3 inflammasome by affecting these regulators. Quercetin, as an anti-inflammatory, antioxidant, analgesic and inflammatory compound, is probably a potential treatment for severe inflammation and one of the main life-threatening conditions in patients with COVID-19.

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Section: Effect Of Quercetin On Sirt1 As Anti-inflammatory Factor and Nlrp3 Inflammasome Inhibitormentioning

confidence: 71%

Anti-inflammatory potential of Quercetin in COVID-19 treatment

2021

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“…Lipopolysaccharide (LPS) is usually applied in animal model to induce systemic inflammation 46 , 47 and also applied in leukocytes or other cells to induce inflammatory reactions or cell damage 48 , 49 . However, LPS is seldom applied in neutrophils to examine transendothelial migration.…”

Section: Discussionmentioning

confidence: 99%

Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration

Huang

Weng

et al. 2020

Sci Rep

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Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD.

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“…Numerous animal models of sepsis (LPS or CLP) have demonstrated common abnormalities: increased level of ROS, decreased antioxidant capacity, and mitochondrial oxidative damage [14,15,74]. LPS-triggered generation of mitochondrial superoxide measured usually with the fluorogenic dye MitoSOX was demonstrated in different cell types, such as microglia [75,76], muscle myoblasts [23], gingival fibroblasts [17], human pulmonary bronchial epithelial cells [77], macrophages [78], and others. In addition, the decline in antioxidative enzymes and glutathione content caused by LPS contributes to the impairment of endogenous antioxidant defense and the subsequent increase in mtROS generation [79][80][81][82][83].…”

Section: Lps Triggers Mtros Generationmentioning

confidence: 99%

Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review

Fock

Парнова

2021

Pharmaceutics

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Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is the most abundant proinflammatory agent. Considerable evidence indicates that LPS challenge inescapably causes oxidative stress and mitochondrial dysfunction, leading to cell and tissue damage. Increased mitochondrial reactive oxygen species (mtROS) generation triggered by LPS is known to play a key role in the progression of the inflammatory response. mtROS at excessive levels impair electron transport chain functioning, reduce the mitochondrial membrane potential, and initiate lipid peroxidation and oxidative damage of mitochondrial proteins and mtDNA. Over the past 20 years, a large number of mitochondria-targeted antioxidants (mito-AOX) of different structures that can accumulate inside mitochondria and scavenge free radicals have been synthesized. Their protective role based on the prevention of oxidative stress and the restoration of mitochondrial function has been demonstrated in a variety of common diseases and pathological states. This paper reviews the current data on the beneficial application of different mito-AOX in animal endotoxemia models, in either in vivo or in vitro experiments. The results presented in our review demonstrate the promising potential of approaches based on mito-AOX in the development of new treatment strategies against Gram-negative infections and LPS per se.

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The protective effect of doxofylline against lipopolysaccharides (LPS)-induced activation of NLRP3 inflammasome is mediated by SIRT1 in human pulmonary bronchial epithelial cells

Abstract: Liu (2020) The protective effect of doxofylline against lipopolysaccharides (LPS)-induced activation of NLRP3 inflammasome is mediated by SIRT1 in human pulmonary bronchial epithelial cells, Artificial Cells,

Cited by 15 publications

References 20 publications

Anti-inflammatory potential of Quercetin in COVID-19 treatment

Anti-inflammatory potential of Quercetin in COVID-19 treatment

Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration

Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review

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