Hepatic Rac1 GTPase contributes to liver-mediated basal immune homeostasis and LPS-induced endotoxemia

Pohlmann, Stephanie; Scheu, Stefanie; Ziegler, Verena; Schupp, Nicole; Henninger, Christian; Fritz, Gerhard

doi:10.1016/j.bbamcr.2018.06.007

Cited by 11 publications

(8 citation statements)

References 65 publications

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“…Furthermore, LPS directly entered the blood through the intestinal barrier, leading to the immune response of macrophages in the liver and triggering an inflammatory signaling mechanism. At last, the low-grade inflammation was produced and the inflammatory factors were released (Pohlmann et al, 2018). In the present study, LPS concentration was reduced and the inflammation factors were decreased significantly (p < 0.01) in the ALD mice by feeding the fermentation broth of P. lobata, L. japonica, and C. pinnatifida, indicating the protective role in the body caused by ALD or further inflammation.…”

Section: Discussionsupporting

confidence: 53%

Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor

Wang

Yang

et al. 2021

Front. Microbiol.

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In this work, we discovered a new fermentation broth that can prevent and regulate alcoholic liver disease (ALD) and intestinal flora, which fermented the mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1. The contents of polyphenols, puerarin, total isoflavones, and amino acids were significantly increased. Animal experiments showed that the fermentation broth could improve the liver indexes of ALD mice model, increase the activity of superoxide dismutase and glutathione in liver tissue, and reduce the level of malondialdehyde (MDA). Furthermore, the fermentation broth can reduce the levels of serum lipopolysaccharide (LPS), inflammatory factors interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Importantly, intestinal flora analysis showed that the fermentation broth could increase the abundance of Lactobacillales and reduce the production of Gram-negative bacteria, thereby reducing the abnormal increase in bacterial diversity caused by alcohol. In conclusion, we may have discovered a new functional food raw material with great application potential. The above findings indicate that the fermentation broth can actively regulate the intestinal flora and improve liver inflammation. The underlying mechanism might be that the fermentation broth could enhance intestinal permeability and reduce the inflammatory signals and LPS transmitted through the gut-liver axis, thereby reducing the oxidative stress and inflammation of the liver caused by alcohol.

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Section: Discussionsupporting

confidence: 53%

Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor

Wang

Yang

et al. 2021

Front. Microbiol.

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“…The inhibition of ROCK also reduced proinflammatory and oxidative stress responses and improved the mitochondrial function in the liver of endotoxemic mice [175]. In contrast, the activity of Rac1 in hepatocytes was suggested as a pathway that continuously modulates inflammatory and immune responses, with both local and systemic repercussions [176].…”

Section: Rho Proteins and Their Impact On Sepsis Outside The Cardiovascular Systemmentioning

confidence: 99%

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Hahmeyer

Silva-Santos

2021

Cells

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Sepsis and septic shock are associated with acute and sustained impairment in the function of the cardiovascular system, kidneys, lungs, liver, and brain, among others. Despite the significant advances in prevention and treatment, sepsis and septic shock sepsis remain global health problems with elevated mortality rates. Rho proteins can interact with a considerable number of targets, directly affecting cellular contractility, actin filament assembly and growing, cell motility and migration, cytoskeleton rearrangement, and actin polymerization, physiological functions that are intensively impaired during inflammatory conditions, such as the one that occurs in sepsis. In the last few decades, Rho proteins and their downstream pathways have been investigated in sepsis-associated experimental models. The most frequently used experimental design included the exposure to bacterial lipopolysaccharide (LPS), in both in vitro and in vivo approaches, but experiments using the cecal ligation and puncture (CLP) model of sepsis have also been performed. The findings described in this review indicate that Rho proteins, mainly RhoA and Rac1, are associated with the development of crucial sepsis-associated dysfunction in different systems and cells, including the endothelium, vessels, and heart. Notably, the data found in the literature suggest that either the inhibition or activation of Rho proteins and associated pathways might be desirable in sepsis and septic shock, accordingly with the cellular system evaluated. This review included the main findings, relevance, and limitations of the current knowledge connecting Rho proteins and sepsis-associated experimental models.

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“…There is some correlation between Rac1 and immunity (156,157). Rac1 regulates the immune homeostasis of the liver, which may exist as an immune checkpoint (158). The activation of Rac1 can drive the pathogenic interaction between epithelial cells and the immune system, which is also the pathological basis of psoriasis (159).…”

Section: Rac1 Participates In Tumor Microenvironment-mediated Immune Escapementioning

confidence: 99%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

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Hepatic Rac1 GTPase contributes to liver-mediated basal immune homeostasis and LPS-induced endotoxemia

Cited by 11 publications

References 65 publications

Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor

Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Rac1, A Potential Target for Tumor Therapy

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