scholarly journals NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

2016 ◽  
Vol 47 (3) ◽  
pp. 910-918 ◽  
Author(s):  
Ismini Lasithiotaki ◽  
Ioannis Giannarakis ◽  
Eliza Tsitoura ◽  
Katerina D. Samara ◽  
George A. Margaritopoulos ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Usual Interstitial Pneumonia ◽  
Lavage Fluid ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Nlrp3 Inflammasomes ◽  
Balf Cell ◽  
Rheumatoid Lung

In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis–usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.

scholarly journals Modulation of the NLRP3 inflammasome by Sars-CoV-2 Envelope protein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mustafa Yalcinkaya ◽  
Wenli Liu ◽  
Mohammad N. Islam ◽  
Andriana G. Kotini ◽  
Galina A. Gusarova ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Protein A ◽  
Lavage Fluid ◽  
Viral Rna ◽  
Poly I:C ◽  
Inflammasome Activation ◽  
E Protein ◽  
Nlrp3 Inflammasome Activation

AbstractDespite the initial success of some drugs and vaccines targeting COVID-19, understanding the mechanism underlying SARS-CoV-2 disease pathogenesis remains crucial for the development of further approaches to treatment. Some patients with severe Covid-19 experience a cytokine storm and display evidence of inflammasome activation leading to increased levels of IL-1β and IL-18; however, other reports have suggested reduced inflammatory responses to Sars-Cov-2. In this study we have examined the effects of the Sars-Cov-2 envelope (E) protein, a virulence factor in coronaviruses, on inflammasome activation and pulmonary inflammation. In cultured macrophages the E protein suppressed inflammasome priming and NLRP3 inflammasome activation. Similarly, in mice transfected with E protein and treated with poly(I:C) to simulate the effects of viral RNA, the E protein, in an NLRP3-dependent fashion, reduced expression of pro-IL-1β, levels of IL-1β and IL-18 in broncho-alveolar lavage fluid, and macrophage infiltration in the lung. To simulate the effects of more advanced infection, macrophages were treated with both LPS and poly(I:C). In this setting the E protein increased NLRP3 inflammasome activation in both murine and human macrophages. Thus, the Sars-Cov-2 E protein may initially suppress the host NLRP3 inflammasome response to viral RNA while potentially increasing NLRP3 inflammasome responses in the later stages of infection. Targeting the Sars-Cov-2 E protein especially in the early stages of infection may represent a novel approach to Covid-19 therapy.

scholarly journals BAFF-driven NLRP3 inflammasome activation in B cells

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Ken-Hong Lim ◽  
Lih-Chyang Chen ◽  
Kate Hsu ◽  
Chia-Ching Chang ◽  
Chia-Yu Chang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Nlrp3 Inflammasome ◽  
Cell Receptor ◽  
Inflammasome Activation ◽  
Additional Function ◽  
B Cell Survival ◽  
Nlrp3 Inflammasome Activation ◽  
B Cell Homeostasis ◽  
Nlrp3 Inflammasomes

Abstract BAFF supports B-cell survival and homeostasis by activating the NF-κB pathway. While NF-κB is also involved in the priming signal of NLRP3 inflammasome, the role of BAFF in NLRP3 inflammasome regulation is unknown. Here we report BAFF engagement to BAFF receptor elicited both priming and activating signals for NLRP3 inflammasomes in primary B cells and B lymphoma cell lines. This induction of NLRP3 inflammasomes by BAFF led to increased NLRP3 and IL-1β expression, caspase-1 activation, IL-1β secretion, and pyroptosis. Mechanistically, BAFF activated NLRP3 inflammasomes by promoting the association of cIAP-TRAF2 with components of NLRP3 inflammasomes, and by inducing Src activity-dependent ROS production and potassium ion efflux. B-cell receptor (BCR) stimulation on the Lyn signaling pathway inhibited BAFF-induced Src activities and attenuated BAFF-induced NLRP3 inflammasome activation. These findings reveal an additional function of BAFF in B-cell homeostasis that is associated with BCR activities.

scholarly journals Age-Dependent Susceptibility to Pulmonary Fibrosis Is Associated with NLRP3 Inflammasome Activation

2016 ◽  
Vol 55 (2) ◽  
pp. 252-263 ◽  
Author(s):  
Heather W. Stout-Delgado ◽  
Soo Jung Cho ◽  
Sarah G. Chu ◽  
Dana N. Mitzel ◽  
Julian Villalba ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Age Dependent

Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis

2020 ◽  
Vol 158 ◽  
pp. 104884 ◽  
Author(s):  
Qing Liang ◽  
Wuyang Cai ◽  
Yaxue Zhao ◽  
Huanbai Xu ◽  
Huirong Tang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Mir-21 Mediates the Inhibitory Effect of Ang (1–7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Na-Na Sun ◽  
Chang-Hui Yu ◽  
Miao-Xia Pan ◽  
Yue Zhang ◽  
Bo-Jun Zheng ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Lung Fibrosis ◽  
Collagen Synthesis ◽  
Inhibitory Effect ◽  
Lung Fibroblasts ◽  
Inflammasome Activation ◽  
Apoptosis Resistance ◽  
Nlrp3 Inflammasome Activation

AbstractMicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1–7) [ACE2/Ang(1–7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1–7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study’s aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1–7) on lung fibroblast apoptosis and collagen synthesis. In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1–7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro, AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1–7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1–7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.

scholarly journals CY-09 Inhibits NLRP3 Inflammasome Activation to Relieve Pain via TRPA1

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Youjia Fan ◽  
Gaici Xue ◽  
Qianbo Chen ◽  
Ye Lu ◽  
Rong Dong ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Pain Treatment ◽  
Underlying Mechanism ◽  
Inflammasome Activation ◽  
Relieve Pain ◽  
Nlrp3 Inflammasome Activation ◽  
Key Factor ◽  
Nlrp3 Inflammasomes

Peripheral tissue damage leads to inflammatory pain, and inflammatory cytokine releasing is the key factor for inducing the sensitization of nociceptors. As a calcium ion channel, TRPA1 plays an important role in pain and inflammation, thus becoming a new type of anti-inflammatory and analgesic target. However, there is no consensus on the role of this channel in mechanical hyperalgesia caused by inflammation. Here, we aim to explore the role and underlying mechanism of the inflammasome inhibitor CY-09 in two classic inflammatory pain models. We evaluated pain behavior on animal models, cytokine levels, intracellular Ca2+ levels, transient TRPA1 expression, NF-κB transcription, and NLPR3 inflammasome activation. Consistently, CY-09 reduced the production of inflammatory cytokines, intracellular Ca2+ levels, and the activation of TRPA1 by inhibiting the activation of inflammasomes, thereby reducing the proinflammatory polarization of macrophages and alleviating animal pain and injury. Importantly, AITC (TRPA1 agonist) significantly reversed the analgesic effect of CY-09, indicating that TRPA1 was involved in the analgesic effect of CY-09. Our findings indicate that CY-09 relieves inflammation and pain via inhibiting TRPA1-mediated activation of NLRP3 inflammasomes. Thus, NLRP3 inflammasome may be a potential therapeutic target for pain treatment and CY-09 may be a pharmacological agent to relieve inflammatory pain, which needs further research.

scholarly journals Distinct effects of complement and of NLRP3- and non-NLRP3 inflammasomes for choroidal neovascularization

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jakob Malsy ◽  
Andrea C Alvarado ◽  
Joseph O Lamontagne ◽  
Karin Strittmatter ◽  
Alexander G Marneros
Keyword(s):  
Choroidal Neovascularization ◽  
Nlrp3 Inflammasome ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Rpe Cells ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Nlrp3 Inflammasomes

NLRP3 inflammasome activation and complement-mediated inflammation have been implicated in promoting choroidal neovascularization (CNV) in age-related macular degeneration (AMD), but central questions regarding their contributions to AMD pathogenesis remain unanswered. Key open questions are (1) whether NLRP3 inflammasome activation mainly in retinal pigment epithelium (RPE) or rather in non-RPE cells promotes CNV, (2) whether inflammasome activation in CNV occurs via NLRP3 or also through NLRP3-independent mechanisms, and (3) whether complement activation induces inflammasome activation in CNV. Here we show in a neovascular AMD mouse model that NLRP3 inflammasome activation in non-RPE cells but not in RPE cells promotes CNV. We demonstrate that both NLRP3-dependent and NLRP3-independent inflammasome activation mechanisms induce CNV. Finally, we find that complement and inflammasomes promote CNV through independent mechanisms. Our findings uncover an unexpected role of non-NLRP3 inflammasomes for CNV and suggest that combination therapies targeting inflammasomes and complement may offer synergistic benefits to inhibit CNV.

scholarly journals Role of NLRP3 Inflammasomes in Neuroinflammation Diseases

2020 ◽  
pp. 1-5
Author(s):  
Sen Lin ◽  
Xifan Mei
Keyword(s):  
Nlrp3 Inflammasome ◽  
Current Knowledge ◽  
Inflammasome Activation ◽  
Protein Signaling ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Inflammatory Immune Response ◽  
Nlrp3 Inflammasomes ◽  
Pro Inflammatory Cytokines

<b><i>Background:</i></b> Inflammasomes are large intracellular multi-protein signaling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1 and pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1β and proIL-18 to produce active forms. The inflammasome complex consists of a nod-like receptor, the adapter apoptosis-associated speck-like protein, and caspase-1. Dysregulation of NLRP3 inflammasome activation is involved in neuroinflammation disease pathogenesis, although its role in SCI development and progression remains controversial due to the inconsistent findings described. <b><i>Summary:</i></b> In this review, we summarize the current knowledge on the contribution of the NLRP3 inflammasome on potential neuroinflammation diseases therapy.

scholarly journals Olive Leaf Extract (OleaVita) Suppresses Inflammatory Cytokine Production and NLRP3 Inflammasomes in Human Placenta

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 970 ◽  
Author(s):  
Yasuaki Kaneko ◽  
Michiya Sano ◽  
Kotomi Seno ◽  
Yuka Oogaki ◽  
Hironori Takahashi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Leaf Extract ◽  
Inflammasome Activation ◽  
Olive Leaf ◽  
Olive Leaf Extract ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory ◽  
Nlrp3 Inflammasomes

The placenta is essential for pregnancy and produces both pro-inflammatory and anti-inflammatory cytokines. Excessive production of inflammatory cytokines, involving interleukin-1β (IL-1β), IL-6, and IL-8, from placental tissues is associated with pregnancy complications. Olive leaf extract has several health benefits, including anti-inflammatory functions. OleaVita is a new commercial olive leaf extract; it is hypothesized to suppress placental inflammation. In human placental tissue culture, OleaVita treatment inhibited the secretion of inflammatory cytokines and NF-κB p65 protein expression. OleaVita also suppressed toll-like receptor ligands-induced IL-1β secretion in human placental tissues. IL-1β is regulated by the NLRP3 inflammasomes, a pivotal regulator of various diseases. OleaVita significantly decreased NLRP3 and pro-IL-1β protein expression, suggesting that it has an inhibitory effect on NLRP3 inflammasome activation. Thus, OleaVita is beneficial as an inhibitor of inflammation and NLRP3 inflammasome activation, and may be used as a supplement for the treatment and prevention of inflammatory diseases.

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