AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection

Gq, Hu; Song, Peixuan; N, Li; Chen, W; Qq, Lei; Sx, Yu; Zhang, Xueji; Ct, Du; Xm, Deng; Wy, Han; Yang, Yao

doi:10.1038/mi.2015.142

Cited by 38 publications

(52 citation statements)

References 39 publications

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“…This positive feedback loop thus sustains AMP expression but can also induce cell proliferation, tissue repair and may therefore also contribute to colorectal cancer development [60]. days post treatment in contrast to the study by Hu et al where this was also happening in naïve AIM2 knockout mice [37,39]. Further experiments indicate that these effects are mediated through an inflammasome/caspase-1-independent inhibitory effect of AIM2 on protein kinase B (PKB/Akt) phosphorylation (Ser473).…”

Section: Aim2 Protects Against Colorectal Cancercontrasting

confidence: 50%

“…Ex vivo genetic knockout leads to increased intestinal organoid formation and growth Man et al 2015 [37] shown to be inflammasome/caspase-1-independent, as pharmacological inhibition of caspase-1 did not lower TEER in these cells whereas Akt inhibition did [39]. Therefore, this study provides a mechanism by which AIM2 mediates Akt phosphorylation, which is a known regulator of TJ proteins in the intestinal epithelium [74,75] …”

Section: Hu Et Al 2015 [39]mentioning

confidence: 81%

“…Whether the observed dysbiosis in this study is also inflammasome-independent remains to be resolved. Yet, dysbiosis in the previously described AIM2 knockout study by Hu et al was suggested to be the result of inflammasome-dependent alterations in epithelial AMP secretion [39]. Also, inflammasomedependent IL-18 secretion has been shown to be essential for intestinal epithelial cell proliferation [7].…”

Section: Resultsmentioning

confidence: 99%

“…Besides protecting against colorectal cancer, it was shown that AIM2 aids in preventing paracellular translocation of Salmonella enterica serovar typhimurium (strain SL1344) through the intestinal epithelium by enhancing the expression of the TJ proteins claudin 3 and occluding [39]. AIM2 knockout mice have increased susceptibility for Salmonella infection that is attributed to increased epithelial translocation rather than decreased intracellular clearance.…”

Section: Aim2 Protects Against Paracellular Salmonella Translocationmentioning

confidence: 99%

“…This effect would be mediated through the regulation of colonic epithelial cell proliferation and modulation of the intestinal microbiome [37,38]. The same inflammasomeindependent mechanism was recently suggested to control intestinal epithelial tight junction (TJ) expression [39]. Here we review the multifunctional role of AIM2 in regulating intestinal homeostasis and its implications for intestinal diseases such as IBD and colorectal cancer (CRC).…”

mentioning

confidence: 99%

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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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Section: Aim2 Protects Against Colorectal Cancercontrasting

confidence: 50%

Section: Hu Et Al 2015 [39]mentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Aim2 Protects Against Paracellular Salmonella Translocationmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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

Vanhove¹,

Peeters²,

Cleynen³

et al. 2017

Inflammasome

View full text Add to dashboard Cite

show abstract

The complex role of AIM2 in autoimmune diseases and cancers

Zhu

Zhao

Chang

et al. 2021

Immunity Inflam & Disease

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Absent in melanoma 2 (AIM2) is a novel member of interferon (IFN)‐inducible PYHIN proteins. In innate immune cells, AIM2 servers as a cytoplasmic double‐stranded DNA sensor, playing a crucial role in the initiation of the innate immune response as a component of the inflammasome. AIM2 expression is increased in patients with systemic lupus erythematosus (SLE), psoriasis, and primary Sjogren's syndrome, indicating that AIM2 might be involved in the pathogenesis of autoimmune diseases. Meanwhile, AIM2 also plays an antitumorigenesis role in an inflammasome independent‐manner. In melanoma, AIM2 is initially identified as a tumor suppressor factor. However, AIM2 is also found to contribute to lung tumorigenesis via the inflammasome‐dependent release of interleukin 1β and regulation of mitochondrial dynamics. Additionally, AIM2 reciprocally dampening the cGAS‐STING pathway causes immunosuppression of macrophages and evasion of antitumor immunity during antibody treatment. To summarize the complicated effect and role of AIM2 in autoimmune diseases and cancers, herein, we provide an overview of the emerging research progress on the function and regulatory pathway of AIM2 in innate and adaptive immune cells, as well as tumor cells, and discuss its pathogenic role in autoimmune diseases, such as SLE, psoriasis, primary Sjogren's syndrome, and cancers, such as melanomas, non‐small‐cell lung cancer, colon cancer, hepatocellular carcinoma, renal carcinoma, and so on, hopefully providing potential therapeutic and diagnostic strategies for clinical use.

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Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

Yang

Zhang

Jin

et al. 2019

J of Cellular Biochemistry

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Absent in melanoma 2 (AIM2) is a critical component in natural immunity system and is closely related to cancer initiation and development. It has been shown that AIM2 inhibited colorectal cancer (CRC) development and cell proliferation. It remains unresolved how AIM2 acts on CRC metastasis. In this study, we assessed migration, invasion ability, and epithelial‐mesenchymal transition (EMT) program upon AIM2 overexpression or knockdown in human CRC cells. Transwell assay demonstrated that upregulation of AIM2 reduced cell migration and invasion. Epithelial marker E‐cadherin was augmented and mesenchymal markers vimentin, as well as Snail, were examined decreased by Western blot, real‐time polymerase chain reaction, and immunofluorescence. Correspondingly, knockdown of AIM2 led to a reverse consequence. In addition, AIM2 regulated Akt phosphorylation and effects of AIM2 on cell invasion and EMT were recovered after administration of Akt inhibitor, suggesting that AIM2 suppressed EMT dependent on Akt pathway. In addition, caspase‐1 inhibitor exposure indicated that AIM2 abrogated EMT through the inflammasome pathway as well. In summary, AIM2 suppressed EMT via Akt and inflammasome pathways in human CRC cells.

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AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection

Cited by 38 publications

References 39 publications

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

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

The complex role of AIM2 in autoimmune diseases and cancers

Absent in melanoma 2 suppresses epithelial‐mesenchymal transition via Akt and inflammasome pathways in human colorectal cancer cells

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