TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Ethical Statement
2.2. Animals and Cells’ Isolation, Culture, and Identification
2.3. Quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR) Analysis
2.4. Western Blotting
2.5. Transmission Electron Microscopy Analysis
2.6. Immunofluorescence Microscopy Analysis
2.7. TUNEL Assay for Detecting Apoptosis
2.8. Measurement of Oxidative Stress
2.9. Statistical Analysis
3. Results
3.1. Generation and Identification of Transgenic Individuals Overexpressing TLR4
3.2. Generation and Identification of Transgenic Individuals Overexpressing TLR4
3.3. Overexpression of TLR4 Promotes the Production of Pro-Inflammatory Cytokines and Oxidative Stress
3.4. Overexpression of TLR4 Leads to Dysfunctional Autophagy
3.5. TLR4 Overexpression Promotes LPS-Induced Apoptosis
3.6. Knockdown of TLR4 Affects Autophagy and the Production of Pro-Inflammatory Cytokines and Oxidative Stress
3.7. Inhibition of TLR4 and Autophagy Alleviates Apoptosis
3.8. NF-κB, p38 MAPK Signaling Pathways, and ROS Are Involved in Autophagy-Mediated Cell Death
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
TLR4 | Toll-like receptor 4 |
LPS | Lipopolysaccharide |
PBMCs | Peripheral blood mononuclear cells |
3-MA | 3-methyladenine |
NF-κB | Nuclear factor kappa-B |
MAPK | Mitogen-activated protein kinase |
MyD88 | Myeloid differentiation factor 88 |
CD14 | Differentiation 14 |
IRAK | IL-1 receptor-associated kinase |
TRIF | TIR domain-containing adaptor-inducing interferon-β |
TRAF | TNF receptor-associated factor |
ATG | Autophagy related gene |
WT | Wild type |
TG | Transgenic |
IL | Interleukin |
TNF | Tumor necrosis factor |
qRT-PCR | Quantitative real-time polymerase chain reaction |
MDA | Malondialdehyde |
ROS | Reactive oxygen species |
BCL-2 | B-cell lymphoma-2 |
BAX | BCL2-Associated X |
RNAi | RNA interference |
TUNEL | TdT-mediated dUTP nick end labelling |
mTOR | Mammalian target of rapamycin |
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Wang, S.; Zhang, K.; Song, X.; Huang, Q.; Lin, S.; Deng, S.; Qi, M.; Yang, Y.; Lu, Q.; Zhao, D.; et al. TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models. Cells 2023, 12, 1769. https://doi.org/10.3390/cells12131769
Wang S, Zhang K, Song X, Huang Q, Lin S, Deng S, Qi M, Yang Y, Lu Q, Zhao D, et al. TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models. Cells. 2023; 12(13):1769. https://doi.org/10.3390/cells12131769
Chicago/Turabian StyleWang, Sutian, Kunli Zhang, Xuting Song, Qiuyan Huang, Sen Lin, Shoulong Deng, Meiyu Qi, Yecheng Yang, Qi Lu, Duowei Zhao, and et al. 2023. "TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models" Cells 12, no. 13: 1769. https://doi.org/10.3390/cells12131769