scholarly journals Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

2016 ◽  
Vol Volume 11 ◽  
pp. 3331-3346 ◽  
Author(s):  
Zhengwang Cao ◽  
Yiliang Fang ◽  
Yonghui Lu ◽  
Fenghua Qian ◽  
Qinglong Ma ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Nlrp3 Inflammasome ◽  
Pulmonary Inflammation ◽  
Oxide Nanoparticles ◽  
Inflammasome Activation ◽  
Nickel Oxide Nanoparticles ◽  
Nlrp3 Inflammasome Activation

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 Targeting NLRP3 Inflammasome Activation in Severe Asthma

2019 ◽  
Vol 8 (10) ◽  
pp. 1615 ◽  
Author(s):  
Efthymia Theofani ◽  
Maria Semitekolou ◽  
Ioannis Morianos ◽  
Konstantinos Samitas ◽  
Georgina Xanthou
Keyword(s):  
Severe Asthma ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Airflow Obstruction ◽  
Inflammasome Activation ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Reversible Airflow Obstruction

Severe asthma (SA) is a chronic lung disease characterized by recurring symptoms of reversible airflow obstruction, airway hyper-responsiveness (AHR), and inflammation that is resistant to currently employed treatments. The nucleotide-binding oligomerization domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome is an intracellular sensor that detects microbial motifs and endogenous danger signals and represents a key component of innate immune responses in the airways. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18 as well as pyroptosis. Accumulating evidence proposes that NLRP3 activation is critically involved in asthma pathogenesis. In fact, although NLRP3 facilitates the clearance of pathogens in the airways, persistent NLRP3 activation by inhaled irritants and/or innocuous environmental allergens can lead to overt pulmonary inflammation and exacerbation of asthma manifestations. Notably, administration of NLRP3 inhibitors in asthma models restrains AHR and pulmonary inflammation. Here, we provide an overview of the pathophysiology of SA, present molecular mechanisms underlying aberrant inflammatory responses in the airways, summarize recent studies pertinent to the biology and functions of NLRP3, and discuss the role of NLRP3 in the pathogenesis of asthma. Finally, we contemplate the potential of targeting NLRP3 as a novel therapeutic approach for the management of SA.

scholarly journals Skin damage induced by zinc oxide nanoparticles combined with UVB is mediated by activating cell pyroptosis via the NLRP3 inflammasome–autophagy–exosomal pathway

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Ying Chen ◽  
Yu-Hsuan Lee ◽  
Bour-Jr Wang ◽  
Rong-Jane Chen ◽  
Ying-Jan Wang
Keyword(s):  
Zinc Oxide ◽  
Nlrp3 Inflammasome ◽  
Zinc Oxide Nanoparticles ◽  
Skin Toxicity ◽  
Oxide Nanoparticles ◽  
Autophagic Flux ◽  
Skin Thickness ◽  
Inflammasome Activation ◽  
Skin Damage ◽  
Nlrp3 Inflammasome Activation

Abstract Background Zinc oxide nanoparticles (ZnONPs) are widely used nanomaterial in personal cosmetics, such as skin creams and sunscreens, due to their whitening properties and strong UV light absorption. However, the safety issues and the hazards of ZnONPs, which can be taken up by the skin and cause skin toxicity, are still unclear. From a chemoprevention point of view, pterostilbene (PT) has been reported to prevent skin damage effectively by its anti-inflammatory and autophagy inducer effect. This study aims to determine the skin toxicity and the potential mechanisms of UVB and ZnONPs exposure and the preventive effect of PT. Results The co-exposure of UVB and ZnONPs elicit NLRP3 inflammasome activation and pyroptosis in keratinocytes. Furthermore, exposure to both UVB and ZnONPs also disrupts cellular autophagy, which increases cell exosome release. In vivo UVB and ZnONPs exposure triggers skin toxicity, as indicated by increased histological injury, skin thickness and transepidermal water loss. Notably, the NLRP3 inflammasome-mediated pyroptosis are also activated during exposure. Topical application of pterostilbene attenuates NLRP3 inflammasome activation and pyroptosis by decreasing ROS generation and mitochondrial ROS (mtROS) levels. In addition to its antioxidant effect, PT also reversed autophagy abnormalities by restoring normal autophagic flux and decreasing NLRP3 inflammasome-loaded exosome release. Conclusions Our findings reveal that ZnONPs induce skin damage in conjunction with UVB exposure. This process involves an interplay of inflammasomes, pyroptosis, autophagy dysfunction, and exosomes in skin toxicity. PT alleviates skin inflammation by regulating the inflammasome–autophagy–exosome pathway, a finding which could prove valuable when further evaluating ZnONPs effects for cosmetic applications.

scholarly journals Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

Immunity ◽  
2021 ◽  
Author(s):  
Hongxu Xian ◽  
Yuan Liu ◽  
Alexandra Rundberg Nilsson ◽  
Raphaella Gatchalian ◽  
Timothy R. Crother ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Nlrp3 Inflammasome ◽  
Pulmonary Inflammation ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation
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