scholarly journals Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells

2021 ◽  
pp. 1-15
Author(s):  
Surabhi Surabhi ◽  
Lana H. Jachmann ◽  
Patience Shumba ◽  
Gerhard Burchhardt ◽  
Sven Hammerschmidt ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Epithelial Cells ◽  
Respiratory Tract ◽  
Nlrp3 Inflammasome ◽  
Lower Respiratory Tract ◽  
Pneumococcal Infections ◽  
Cell Death Pathways ◽  
Epithelial Cell Death

Epithelial cells play a crucial role in detection of the pathogens as well as in initiation of the host immune response<i>. Streptococcus pneumoniae</i> (pneumococcus) is a typical colonizer of the human nasopharynx, which can disseminate to the lower respiratory tract and subsequently cause severe invasive diseases such as pneumonia, sepsis, and meningitis. Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is produced by pneumococci as a product of the pyruvate oxidase SpxB. However, its role as a virulence determinant in pneumococcal infections of the lower respiratory tract is not well understood. In this study, we investigated the role of pneumococcal-derived H<sub>2</sub>O<sub>2</sub> in initiating epithelial cell death by analyzing the interplay between 2 key cell death pathways, namely, apoptosis and pyroptosis. We demonstrate that H<sub>2</sub>O<sub>2</sub> primes as well as activates the NLRP3 inflammasome and thereby mediates IL-1β production and release. Furthermore, we show that pneumococcal H<sub>2</sub>O<sub>2</sub> causes cell death via the activation of both apoptotic as well as pyroptotic pathways which are mediated by the activation of caspase-3/7 and caspase-1, respectively. However, H<sub>2</sub>O<sub>2</sub>-mediated IL-1β release itself occurs mainly via apoptosis.

scholarly journals Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5349
Author(s):  
Mayes Alswady-Hoff ◽  
Johanna Samulin Erdem ◽  
Santosh Phuyal ◽  
Oskar Knittelfelder ◽  
Animesh Sharma ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Health Effects ◽  
Stress Responses ◽  
Cell Stress ◽  
Lipid Classes ◽  
Long Term Effects ◽  
Cell Death Pathways ◽  
Pulmonary Epithelial Cells

There is little in vitro data available on long-term effects of TiO2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.

scholarly journals The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sung-Yoon Kang ◽  
Hyojung Kim ◽  
Sungwon Jung ◽  
Sang Min Lee ◽  
Sang Pyo Lee
Keyword(s):  
Principal Component Analysis ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Beta Diversity ◽  
Lower Respiratory Tract ◽  
Principal Component ◽  
Control Group ◽  
Flexible Bronchoscope ◽  
Bronchial Washing

Abstract Background The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. Results Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. Conclusions The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.

scholarly journals Cell Death Pathways and Viruses: Role of microRNAs

2021 ◽  
Author(s):  
Javid Sadri Nahand ◽  
Layla Shojaie ◽  
Seyed Amirreza Akhlagh ◽  
Mohammad Saeid Ebrahimi ◽  
Hamid Reza Mirzaei ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Death Pathways

scholarly journals Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide

2008 ◽  
Vol 102 (12) ◽  
pp. 2130-2135 ◽  
Author(s):  
Louise K. Charkoudian ◽  
Tzvete Dentchev ◽  
Nina Lukinova ◽  
Natalie Wolkow ◽  
Joshua L. Dunaief ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

Sialodacryoadenitis Virus-associated Lesions in the Lower Respiratory Tract of Rats

1986 ◽  
Vol 23 (3) ◽  
pp. 278-286 ◽  
Author(s):  
Z. W. Wojcinski ◽  
D. H. Percy
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Viral Antigen ◽  
Wistar Rats ◽  
Immunofluorescence Microscopy ◽  
Sendai Virus ◽  
Post Inoculation ◽  
Mycoplasma Pulmonis ◽  
Associated Lesions

Eight- to 10-week-old outbred Wistar rats were inoculated intranasally with 1029 medium mouse lethal infective doses of sialodacryoadenitis (SDA) virus. Sham inoculated control rats and challenged rats were killed at 1 day intervals for the first 8 days, then on days 10, 12, 14, and 20. Typical lesions associated with SDA were seen microscopically in the salivary and lacrimal glands of inoculated rats. In addition, laryngitis, tracheitis, bronchitis, bronchiolitis, and multifocal alveolitis were present during the acute stages of the disease. Viral antigen was demonstrated in epithelial cells lining airways by immunofluorescence microscopy. SDA virus was recovered from the lower respiratory tract from days 2 to 6 post-inoculation (PI). Serum antibodies to SDA virus, but not to Sendai virus or Mycoplasma pulmonis were present in rats tested at day 20 PI. These findings demonstrate that during the acute stages of the disease, significant lesions do occur in the lower respiratory tract of SDA virus-infected rats.

scholarly journals The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development

2020 ◽  
Vol 295 (24) ◽  
pp. 8325-8330 ◽  
Author(s):  
Sannula Kesavardhana ◽  
R. K. Subbarao Malireddi ◽  
Amanda R. Burton ◽  
Shaina N. Porter ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Cell Death ◽  
Nucleic Acids ◽  
Influenza A Virus ◽  
Nlrp3 Inflammasome ◽  
Influenza A ◽  
Defense Responses ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Perinatal Lethality

Z-DNA-binding protein 1 (ZBP1) is an innate immune sensor of nucleic acids that regulates host defense responses and development. ZBP1 activation triggers inflammation and pyroptosis, necroptosis, and apoptosis (PANoptosis) by activating receptor-interacting Ser/Thr kinase 3 (RIPK3), caspase-8, and the NLRP3 inflammasome. ZBP1 is unique among innate immune sensors because of its N-terminal Zα1 and Zα2 domains, which bind to nucleic acids in the Z-conformation. However, the specific role of these Zα domains in orchestrating ZBP1 activation and subsequent inflammation and cell death is not clear. Here we generated Zbp1ΔZα2/ΔZα2 mice that express ZBP1 lacking the Zα2 domain and demonstrate that this domain is critical for influenza A virus–induced PANoptosis and underlies perinatal lethality in mice in which the RIP homotypic interaction motif domain of RIPK1 has been mutated (Ripk1mRHIM/mRHIM). Deletion of the Zα2 domain in ZBP1 abolished influenza A virus–induced PANoptosis and NLRP3 inflammasome activation. Furthermore, deletion of the Zα2 domain of ZBP1 was sufficient to rescue Ripk1mRHIM/mRHIM mice from perinatal lethality caused by ZBP1-driven cell death and inflammation. Our findings identify the essential role of the Zα2 domain of ZBP1 in several physiological functions and establish a link between Z-RNA sensing via the Zα2 domain and promotion of influenza-induced PANoptosis and perinatal lethality.

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