TLR9 mediates the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation

Zhao, Cui-Cui; Xie, Qiu-Meng; Xu, Jianming; Yan, Xinfeng; Fan, Xiaoning; Wu, Hui-Mei

doi:10.1016/j.molimm.2020.06.016

Cited by 19 publications

(15 citation statements)

References 42 publications

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“…In line with these reports, our immunohistochemical analysis of TLR3 showed a significant increase in dKO retina, supporting the modulatory effect of TLR3 in times of oxidative stress. The release of mtDNA and oxidative stress have long been hypothesized in AMD progression, and recent studies have highlighted their tight regulation with TLR9 signaling and inflammation [57][58][59]. Previously, we showed that elevated oxidative stress results in incomplete mitochondrial repair mechanisms and an accumulation of oxidized undigested mitophagy aggregates [60].…”

Section: Discussionmentioning

confidence: 87%

“…This suggests that both TLR3 and TLR9 can also respond to local oxidative stress and be associated with distinctive changes in selective TLR expression in the retina, e.g., by initiating an innate immune response. In addition, oxidative stress and TLR9 have been shown to mediate the NLRP3 inflammasome [19,58]. In particular, the activation of the NLRP3 inflammasome has been linked with inflammation and AMD pathogenesis [19,62].…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Gurubaran

Heloterä

Marry

et al. 2021

Biology

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Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Gurubaran

Heloterä

Marry

et al. 2021

Biology

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“…This NF‐κB activation induced by CpG DNA includes the p50 and p65 subunits but not p52 17 . It has been recently reported that TLR9 may mediate inflammation through the NLRP3 pathway 64 …”

Section: Immunogenicity Of Bacterial Dna Containing Cpg Motifsmentioning

confidence: 97%

The role of bacterial DNA containing CpG motifs in diseases

Zhou

Deng

2021

Journal of Leukocyte Biology

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Bacterial DNA containing unmethylated CpG motifs can activate immune cells to release proinflammatory cytokines. Here, the role of bacterial DNA containing CpG motifs in diseases with a focus on arthritis is discussed. Our studies demonstrate that the intraarticular injection of bacterial DNA and oligodeoxynucleotides containing CpG motifs (CpG ODN) induced arthritis. The induction of arthritis involves the role of macrophages over other cells such as neutrophils, NK cells, and lymphocytes. TNF-and TNFRI play an important role in the development of arthritis. NF-B also plays a critical regulatory role in arthritis. Systemic anti-inflammatory treatment, along with antibiotic therapy, has beneficial effects on the course and the outcome of bacterial arthritis. Thus, future treatment strategies for bacterial arthritis should include attempts to minimizing bacterial growth while blocking the proinflammatory effects of the bacterial DNA. Significant therapeutic efficiency has also been shown by CpG ODN-mediated Th1 immune activation in mouse models of cancer, infectious disease, and allergy/asthma.

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“…TLR9-mediated NLRP3 inflammasome activation has been described in several disease models [68][69][70]. However, the mechanisms of this interrelationship have not been fully elucidated.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Mitochondrial DNA‐Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease

Jin

Armando

et al. 2021

Oxidative Medicine and Cellular Longevity

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The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.

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TLR9 mediates the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation

Cited by 19 publications

References 42 publications

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

The role of bacterial DNA containing CpG motifs in diseases

Mitochondrial DNA‐Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease

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