Gut–Liver Axis: Role of Inflammasomes

Bawa, Manan; Saraswat, Vivek A.

doi:10.1016/j.jceh.2013.03.225

Cited by 40 publications

(39 citation statements)

References 108 publications

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“…Among those 341 increased proteins, 22 proteins were probably involved in the activation of NOD‐like receptor signaling pathway. NLRP3 inflammasome, one of the common studied NOD‐like receptor family, has been revealed as the mediator of LPS‐induced acute liver injury . We demonstrated that hepatocytes could uptake macrophage‐derived exosomes and subsequently NLRP3 inflammasome was activated.…”

Section: Introductionmentioning

confidence: 83%

Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

et al. 2018

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Exosomes are typically involved in cellular communication and signaling. Macrophages play a key role in lipopolysaccharide (LPS)‐induced sepsis. However, the molecular comparison of exosomes derived from LPS‐induced macrophage has not been well analyzed. The macrophage‐exosomes are validated and the protein composition of those exosomes are investigated by isobaric tags for relative and absolute quantification (iTRAQ) mass spectrometry. A total of 5056 proteins are identified in macrophage‐exosomes. We discovered 341 increased proteins and 363 reduced proteins in LPS‐treated macrophage‐exosomes compared with control exosomes. In addition, gene ontology analysis demonstrates that macrophage‐exosomes proteins are mostly linked to cell, organelle, extracellular region, and membrane. The bioinformatics analysis also indicates that these proteins are mainly involved in cellular process, single‐organism process, metabolic process, and biological regulation. Among these 341 upregulated proteins, Kyoto Encyclopedia of Genes and Genomes analysis reveals that 22 proteins are involved in the NOD‐like receptor signaling pathway. Finally, hepatocytes can uptake macrophage‐exosomes and subsequently NLRP3 inflammasome is activated in vitro and in vivo. These data emphasize the fundamental importance of macrophage‐exosomes in sepsis‐induced liver injury. Therefore, the iTRAQ proteomic strategy brings new insights into macrophage‐derived exosomes. It may improve our understanding of macrophage‐exosomes’ functions and their possible use as therapeutic targets for sepsis.

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Section: Introductionmentioning

confidence: 83%

Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

et al. 2018

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“…In the context of diseases of unknown etiology and with no available prevention or cure, man-microbe symbiosis was shown to be durably altered in conjunction with reciprocal aggravating signals. For instance, altered microbiota could promote intestinal hyperpermeability and inflammation, the latter promoting oxidative stress aggravating microbiota alteration [15][16][17]). …”

Section: What Are the Tools For Studying Microbiota?mentioning

confidence: 99%

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

2017

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Summary From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage microbiome knowledge and tools. The rationale for our working group has been structured around four domains of innovation that could derive from ongoing efforts in deciphering the interactions between human cells and intestinal microbiome as a central component of human health, namely: (1) development of stratification and monitoring tools; (2) identification of new target and drug discovery, as a part of our supra-genome; (4) exploitation of microbiota as a therapeutic target that can be modulated; (4) and finally as a source of live biotherapeutics and adjuvants. These four streams will exemplify how microbiota has changed the way we consider a wide range of chronic and incurable diseases and the consequences of long-lasting dysbiosis. In-depth microbiota analysis is opening one of the broadest fields of investigation for improving human and animal health and will be a source of major therapeutic innovations for tackling today's medical unmet needs. We thus propose a range of recommendations for basic researchers, care givers as well as for hea...

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“…In the human gut, AIM2 is predominantly expressed in macrophages and epithelial cells throughout the small and large intestine [16][17][18]. AIM2 is best known as an intracellular danger sensor present in a number of tissues with strong immune regulation other than the gut, such as the lungs [19][20][21], joints [22,23], skin [24,25], liver [26][27][28], brain [29,30] and gingiva [31,32]. Furthermore, AIM2 has been associated with (auto-)…”

Section: Absent In Melanomamentioning

confidence: 99%

Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

Vanhove¹,

Peeters²,

Cleynen³

et al. 2017

Inflammasome

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epithelial cell proliferation, tight junction expression and the microbiome. Therefore, AIM2 plays a significant role in maintaining intestinal homeostasis. This review focuses on the multifunctional role of AIM2 in intestinal homeostasis by regulating intestinal immunity and preventing colorectal cancer development.Keywords: Inflammasome, Inflammatory Bowel Disease, Colorectal Cancer, Proliferation, Antimicrobial Peptides, Intestinal Microbiota, Tight Junctions 1 Introduction Inflammasomes in intestinal homeostasisRegulation of normal intestinal mucosal function is essential for the host's survival. The continuous interaction between the xenogenous and microbial environment, and the gut's immune system demands optimal regulation. Impaired functioning may result in intestinal barrier dysfunction, dysbiosis, inflammation and carcinogenesis [1,2]. Inflammasomes are important immune regulators for intestinal homeostasis that allow recruitment and activation of the inflammatory caspase-1, upon stimulation by a wide variety of triggers. This will activate downstream mediators, including interleukin-1β (IL-1β) and interleukin-18 (IL-18), that, in combination with other alarm molecules (eg. high mobility group box 1, HMGB1) are the driving force of inflammation [3]. Furthermore, activated caspase-1 can also trigger pyroptosis, a specific form of cell death associated with inflammation. In contrast to apoptosis, pyroptosis will release cytoplasmic components into the extracellular space that can fuel inflammatory processes in adjacent cells [4][5][6]. This distinction is important as apoptosis is characterized by chromatin condensation, cell vacuolization and phagocytosis Abstract: The intestinal mucosa is a difficult environment to maintain homeostasis as it is constantly challenged by microbial and food antigens. Maintaining an intact epithelial barrier, a continuous turnover of intestinal epithelial cells and normobiosis of the gut microbiota are essential components to prevent intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Inflammasomes are critical immune regulators that are involved in all of these processes. They are multiprotein complexes able to assemble upon interaction with a noxious stimulus that will subsequently lead to caspase-1 activation. Activated caspase-1 will orchestrate the maturation and release of proinflammatory cytokines IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. Both cytokine release and pyroptosis are initiated after detection of molecular patterns by a distinct inflammasome sensor protein. Absent in melanoma 2 (AIM2) is such an inflammasome sensor that specifically responds to the presence of double stranded DNA (dsDNA) in the cytoplasm, leading to the recruitment and activation of caspase-1. Recent studies revealed additional roles of AIM2 in controlling Review ArticleOpen Access

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Gut–Liver Axis: Role of Inflammasomes

Cited by 40 publications

References 108 publications

Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

Proteomic Profiling of LPS‐Induced Macrophage‐Derived Exosomes Indicates Their Involvement in Acute Liver Injury

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

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