Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis

Chen, Sainan; Tan, Ying; Xiao, Xiaochan; Li, Qian; Wu, Qi; Peng, You-You; Ren, Jun; Dong, Maolong

doi:10.1038/s41401-020-00597-x

Cited by 64 publications

(32 citation statements)

References 51 publications

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“…During sepsis, the rate of cellular death increases due to the activation of the mitochondrial apoptosis pathway [ 65 ]. In the current study, we also observed an increase in the apoptotic rate in liver and heart tissues, consistent with recent studies [ 59 , 66 ]. The induction of the pathophysiological process of sepsis may result from both an apoptosis-induced decrease in the number of immune cells and an immunosuppressive effect of apoptotic cells [ 65 ].…”

Section: Discussionsupporting

confidence: 93%

A low direct electrical signal attenuates oxidative stress and inflammation in septic rats

et al. 2021

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Electrical stimulation is proposed to exert an antimicrobial effect according to studies performed using bacterial and cell cultures. Therefore, we investigated the effects of electrification on inflammation in septic rats. Twenty-eight male Wistar albino rats were divided into 4 groups: healthy control (C), electrified healthy (E), sepsis (S), and electrified sepsis (SE) groups. Staphylococcus aureus (1 x 109 colonies) in 1 ml of medium was intraperitoneally injected into rats to produce a sepsis model. The rats in the E and SE groups were exposed to a low direct electrical signal (300 Hz and 2.5 volts) for 40 min and 1 and 6 h after bacterial infection. Immediately after the second electrical signal application, blood and tissue samples of the heart, lung, and liver were collected. An antibacterial effect of a low direct electrical signal was observed in the blood of rats. The effects of electrical signals on ameliorating changes in the histological structure of tissues, blood pH, gases, viscosity and cell count, activities of some important enzymes, oxidative stress parameters, inflammation and tissue apoptosis were observed in the SE group compared to the S group. Low direct electrical signal application exerts antibacterial, antioxidant, anti-inflammatory and antiapoptotic effects on septic rats due to the induction of electrolysis in body fluids without producing any tissue damage.

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Section: Discussionsupporting

confidence: 93%

A low direct electrical signal attenuates oxidative stress and inflammation in septic rats

et al. 2021

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“…The observed LPS-mediated hepatic response was dependent on TLR4 and independent of TLR2, as was the level of pulmonary inflammation. LPS-induced liver inflammation has been shown to depend on TLR4 when comparing WT and TLR4−/− mice exposed to LPS and similar responses were provoked in primary hepatic Kupffer cells isolated from the mice following LPS exposure [ 71 ]. This suggests that the TLR4-dependent liver inflammation was initiated by a direct interaction between LPS and Kupffer cells.…”

Section: Discussionmentioning

confidence: 99%

Nanomaterial- and shape-dependency of TLR2 and TLR4 mediated signaling following pulmonary exposure to carbonaceous nanomaterials in mice

et al. 2021

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Background Pulmonary exposure to high doses of engineered carbonaceous nanomaterials (NMs) is known to trigger inflammation in the lungs paralleled by an acute phase response. Toll-like receptors (TLRs), particularly TLR2 and TLR4, have recently been discussed as potential NM-sensors, initiating inflammation. Using Tlr2 and Tlr4 knock out (KO) mice, we addressed this hypothesis and compared the pattern of inflammation in lung and acute phase response in lung and liver 24 h after intratracheal instillation of three differently shaped carbonaceous NMs, spherical carbon black (CB), multi-walled carbon nanotubes (CNT), graphene oxide (GO) plates and bacterial lipopolysaccharide (LPS) as positive control. Results The LPS control confirmed a distinct TLR4-dependency as well as a pronounced contribution of TLR2 by reducing the levels of pulmonary inflammation to 30 and 60% of levels in wild type (WT) mice. At the doses chosen, all NM caused comparable neutrophil influxes into the lungs of WT mice, and reduced levels were only detected for GO-exposed Tlr2 KO mice (35%) and for CNT-exposed Tlr4 KO mice (65%). LPS-induced gene expression was strongly TLR4-dependent. CB-induced gene expression was unaffected by TLR status. Both GO and MWCNT-induced Saa1 expression was TLR4-dependent. GO-induced expression of Cxcl2, Cxcl5, Saa1 and Saa3 were TLR2-dependent. NM-mediated hepatic acute phase response in terms of liver gene expression of Saa1 and Lcn2 was shown to depend on TLR2 for all three NMs. TLR4, in contrast, was only relevant for the acute phase response caused by CNTs, and as expected by LPS. Conclusion TLR2 and TLR4 signaling was not involved in the acute inflammatory response caused by CB exposure, but contributed considerably to that of GO and CNTs, respectively. The strong involvement of TLR2 in the hepatic acute phase response caused by pulmonary exposure to all three NMs deserves further investigations.

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“…Recent experiments have proven that inhibiting the TLR4/MyD88/NF-κB signaling pathway can reduce liver inflammation. 47 , 48 Previous transcriptome sequencing results in HSCs also showed that changes in the expression of CD73 will have a significant impact on the NF-κB and Toll-like receptor signaling pathways. In this study, we observed that the expression of the TLR4/MyD88/NF-κB signaling pathway was upregulated under EtOH stimulation, both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

CD73 Attenuates Alcohol-Induced Liver Injury and Inflammation via Blocking TLR4/MyD88/NF-κB Signaling Pathway

Liu¹,

Wu²,

Qian³

et al. 2022

JIR

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Background: Alcoholic liver disease (ALD) is liver damage caused by long-term drinking. Inflammation plays a central role in the progression of ALD. CD73 is a ubiquitously expressed glycosylphosphatidylinositol-anchored glycoprotein that is a key enzyme that converts ATP into adenosine. Evidence has shown that CD73 plays an important role in many diseases, but the role and mechanism of CD73 in alcohol-induced liver injury and inflammation is still unclear. Methods: The alcohol-induced liver injury and inflammation mouse model was established. The rAAV9-CD73 was used to overexpress CD73. Isolation of primary macrophages (MΦ) from the liver was conducted. The effects of CD73 on alcohol-induced liver injury and inflammation were evaluated by quantitative real-time PCR, Western blotting, ELISA, and immunohistochemical assay. Flow cytometry was used to detect the cell cycle and apoptosis. Results: Our results showed that overexpression of CD73 can reduce alcohol-induced liver damage, lipid accumulation, and the secretion of inflammatory cytokines. pEX3-CD73 can promote RAW264.7 cells proliferation and inhibit apoptosis via suppressing the activation of TLR4/MyD88/NF-κB signaling pathway. Inhibition of TLR4 further enhanced the antiinflammatory effect of overexpression of CD73. Conclusion: Overexpression of CD73 can reduce alcohol-induced liver injury and inflammation. CD73 may serve as a potential therapeutic target for ALD.

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Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis

Cited by 64 publications

References 51 publications

A low direct electrical signal attenuates oxidative stress and inflammation in septic rats

A low direct electrical signal attenuates oxidative stress and inflammation in septic rats

Nanomaterial- and shape-dependency of TLR2 and TLR4 mediated signaling following pulmonary exposure to carbonaceous nanomaterials in mice

CD73 Attenuates Alcohol-Induced Liver Injury and Inflammation via Blocking TLR4/MyD88/NF-κB Signaling Pathway

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