Caspase-11 attenuates gastrointestinal inflammation and experimental colitis pathogenesis

Williams, Tere; Leeth, Rachel A.; Rothschild, Daniel E.; McDaniel, Dylan K.; Coutermarsh-Ott, Sheryl; Simmons, Alysha; Kable, Kye H.; Heid, Bettina; Allen, Irving C.

doi:10.1152/ajpgi.00234.2014

Cited by 48 publications

(83 citation statements)

References 56 publications

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“…Recent studies have also demonstrated a requirement for caspase 11 in mediating resistance against dextran sulfate sodium (DSS)-induced intestinal inflammation in mice 69-71 . Whether IL-1β and IL-18 are contributing factors in this case is contentious, with both similar and reduced levels of IL-1β and IL-18 being reported in caspase 11-deficient mice treated with DSS compared with treated wild-type mice 70, 71 . Differences in gut microbiota harboured by mice housed in different facilities and differences in experimental conditions could account for these discrepancies.…”

Section: Pyroptosis and Other Effector Functionsmentioning

confidence: 75%

Converging roles of caspases in inflammasome activation, cell death and innate immunity

2015

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Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes to direct inflammasome and interferon (IFN) responses to fine tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.

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Section: Pyroptosis and Other Effector Functionsmentioning

confidence: 75%

Converging roles of caspases in inflammasome activation, cell death and innate immunity

2015

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“…Here we utilized Irak-m −/− mice in an acute colitis model induced with 5% DSS (Okayasu et al, 1990). This is a standard model utilized previously by our laboratory in similar studies evaluating mediators of innate immunity in IBD (Williams et al, 2015a, Williams et al, 2015b, Allen et al, 2012, Allen et al, 2010). We found that Irak-m −/− mice are protected in this experimental colitis model (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In order to assess acute experimental colitis, mice were given either 3 or 5% DSS dissolved in drinking water available ad libitum for 5 days as previously described (Williams et al, 2015b, Schneider, 2013). On day 5, mice were withdrawn from DSS and given regular drinking water ad libitum until euthanasia was performed on day 7.…”

Section: Methodsmentioning

confidence: 99%

“…On day 5, mice were withdrawn from DSS and given regular drinking water ad libitum until euthanasia was performed on day 7. Cumulative semi quantitative clinical scores for acute experimental colitis were assessed as previously described (Williams et al, 2015b, Schneider, 2013). Tumorigenesis was induced via a single intraperitoneal (i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…Blinded to treatment and mouse genotype, examination of histopathology was conducted by a board-certified veterinary pathologist (T.L.). Colon H&E sections were evaluated and scored as previously described (Williams et al, 2015b). Additional colon sections were further prepared for immunohistochemistry and stained with anti -β-catenin and DAPI to determine β-catenin levels in the AOM + DSS studies.…”

Section: Methodsmentioning

confidence: 99%

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Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

et al. 2017

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Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD) and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m−/− mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m−/− animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m−/− mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT), increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m−/− mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.

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The role of the microbiome and the NLRP3 inflammasome in the gut and lung

Donovan

Liu

Shen

et al. 2020

Journal of Leukocyte Biology

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The nucleotide‐binding oligomerization domain (NOD)‐like receptor (NLR) family, pyrin domain‐containing protein 3 (NLRP3) inflammasome, is one of the most well‐characterized inflammasomes, activated by pathogen‐associated molecular patterns and damage‐associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut–lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut–lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

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Caspase-11 attenuates gastrointestinal inflammation and experimental colitis pathogenesis

Abstract: IC. Caspase-11 attenuates gastrointestinal inflammation and experimental colitis pathogenesis.

Cited by 48 publications

References 56 publications

Converging roles of caspases in inflammasome activation, cell death and innate immunity

Converging roles of caspases in inflammasome activation, cell death and innate immunity

Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

The role of the microbiome and the NLRP3 inflammasome in the gut and lung

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