DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer

Paludan, Søren R; Reinert, Line S.; Hornung, Veit

doi:10.1038/s41577-018-0117-0

Cited by 136 publications

(145 citation statements)

References 165 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…13,16,18 This inconsistency may be explained by tissue-specific expression, patients' ethnicities, inconsistent assay methods and data analysis methods. 30,31 Here we used the ONCOMINE cancer microarray database to show that the expression of SPON2 is significantly higher in GC tissues compared with those in matched para-tumorous tissues. IHC analysis demonstrated that high expression of SPON2 was significantly associated with T-and N-staging, OS and DFS, which is consistent with the findings of Jin et al 32 Moreover, SPON2 expression was significantly increased in GC tissues from patients with metastasis and relapse 3 years after surgery, suggesting that SPON2 overexpression is associated with relapse and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells

Feng

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Spondin 2 (SPON2), a member of the Mindin F‐Spondin family, identifies pathogens, activates congenital immunity and promotes the growth and adhesion of neurons as well as binding to their receptors, but its role in promoting or inhibiting tumour metastasis is controversial. Here, we investigated its expression levels and mechanism of action in gastric cancer (GC). Western blotting and GC tissue arrays were used to determine the expression levels of SPON2. ELISAs were performed to measure the serum levels of SPON2 in patients with GC. Two GC cell lines expressing low levels of SPON2 were used to analyse the effects of regulating SPON2 expression on proliferation, migration, invasion, the cell cycle and apoptosis. The results revealed that SPON2 was highly expressed in GC tissues from patients with relapse or metastasis. The levels of SPON2 in sera of patients with GC were significantly higher compared with those of healthy individuals and patients with atrophic gastritis. Knockdown of SPON2 expression significantly inhibited the proliferation, migration and invasion of GC cells in vitro and in vivo. Down‐regulation of SPON2 arrested the cell cycle in G1/S, accelerated apoptosis through the mitochondrial pathway and inhibited the epithelial‐mesenchymal transition by blocking activation of the ERK1/2 pathway. In summary, this study suggests that SPON2 acts as an oncogene in the development of GC and may serve as a marker for the diagnosing GC as well as a new therapeutic target for GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells

Feng

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Previous work suggested that parkin is a negative regulator of the IFN pathway (10,11). To examine the role of parkin in IFN production during IAV infection, we infected Mif +/+ and Parkin -/mice with IAV and measured IFN-λ, which is released earlier and at higher concentrations than the other IFNs (8,33).…”

Section: Attenuated Mif Expression Results In Less Parkin In Lungs Prmentioning

confidence: 99%

“…Inflammation is controlled by inhibiting several pathways, such as the stimulator of IFN genes (STING) pathway. The STING pathway can be activated by intracellular DNA, including that from mitochondrial sources (10). The critical mitophagy protein parkin was recently shown to diminish STING-mediated inflammation and, thus, the production of type I IFNs, such as IFN-α/β; however, its contribution to IAV infection is not known (11,12).…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor enhances influenza-associated mortality in mice

Smith¹,

Tyrell²,

Kulkarni³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

show abstract

“…Defective clearance of necroptotic cells have been proposed to initiate in ammatory responses by the release of danger-associated molecular patterns (DAMPs). DNA acts as a major DAMP and is sensed in endolysosomes by Toll-like receptor 9 (TLR9) and in the cytoplasm by cyclic GMP-AMP (cGAMP) synthase (cGAS), inducing the production of type I and type III IFNs and eliciting strong in ammatory responses [19,20]. Several studies have demonstrated that patients with SLE have elevated circulating IFNs [21][22][23], whose signaling contributes to the steady-state expression of MLKL and the initiation of necroptosis, which not only causes tissue damage [6], but may also form a dynamic feedback loop in SLE pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity

Zhang

Jie

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods: Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value. Results: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r=0.3577, p=0.0237), erythrocyte sedimentation rate (ESR) (r=0.4091, p=0.0043), serum immunoglobulin G (IgG) concentration (r=0.3546, p=0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r=0.3945, p=0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779 - 0.9775, p<0.001) to discriminate SLE from controls.Conclusions: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

show abstract

DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer

Cited by 136 publications

References 165 publications

Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells

Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells

Macrophage migration inhibitory factor enhances influenza-associated mortality in mice

Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity

Contact Info

Product

Resources

About