Interferons at the crossroad of cell death pathways during gastrointestinal inflammation and infection

Stolzer, Iris; Ruder, Barbara; Günther, Claudia

doi:10.1016/j.ijmm.2021.151491

Cited by 7 publications

(6 citation statements)

References 191 publications

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“…Günther et al ( 2019 ) reported that in the gut epithelium, IFNλ causes the expression of mixed lineage kinase domain like pseudokinase ( Mlkl ) and Stat1 , which leads to increased necroptosis in PCs, controlled by caspase8 (CASP8) (Fig 5B ) (Günther et al , 2019 ). This increased PC death has been seen in CD patients, in whom also higher levels of IFNλ were observed in serum and inflamed ileal tissue (Stolzer et al , 2021 ).…”

Section: Pcs In Pathologymentioning

confidence: 61%

Paneth cells as the cornerstones of intestinal and organismal health: a primer

2022

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Paneth cells are versatile secretory cells located in the crypts of Lieberkühn of the small intestine. In normal conditions, they function as the cornerstones of intestinal health by preserving homeostasis. They perform this function by providing niche factors to the intestinal stem cell compartment, regulating the composition of the microbiome through the production and secretion of antimicrobial peptides, performing phagocytosis and efferocytosis, taking up heavy metals, and preserving barrier integrity. Disturbances in one or more of these functions can lead to intestinal as well as systemic inflammatory and infectious diseases. This review discusses the multiple functions of Paneth cells, and the mechanisms and consequences of Paneth cell dysfunction. It also provides an overview of the tools available for studying Paneth cells.

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Section: Pcs In Pathologymentioning

confidence: 61%

Paneth cells as the cornerstones of intestinal and organismal health: a primer

2022

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“… 27 We included necrostatin-1, 28 a selective and potent inhibitor of the necroptosis executioner RIPK1, to clarify whether necroptosis is responsible for the IFN-β-induced cell death. 29 These studies demonstrated that IFN-β treatment resulted in cell death that could be blocked by necrostatin-1 ( figure 4C, D ).…”

Section: Resultsmentioning

confidence: 88%

IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling

Chiriac,

Hracsko,

Günther

et al. 2023

Gut

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ObjectiveWe sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis.DesignExperimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation. We further used RNA-sequencing (RNA-Seq), RNAScope and Gene Ontology analysis, western blot analysis and co-immunoprecipitation, confocal microscopy and intestinal epithelial cell (IEC)-derived three-dimensional organoids to investigate the underlying molecular mechanisms. Results were validated using samples from patients with IBD and non-IBD control subjects by a combination of RNA-Seq, organoids and immunostainings.ResultsIn IBD,IL20levels were induced during remission and were significantly higher in antitumour necrosis factor responders versus non-responders. IL-20RA and IL-20RB were present on IECs from patients with IBD and IL-20-induced STAT3 and suppressed interferon (IFN)-STAT2 signalling in these cells. In IBD, experimental dextran sulfate sodium (DSS)-induced colitis and mucosal healing, IECs were the main producers of IL-20. Compared with wildtype controls,Il20−/−, Il20ra−/−andIl20rb−/−mice were more susceptible to experimental DSS-induced colitis. IL-20 deficiency was associated with increased IFN/STAT2 activity in mice and IFN/STAT2-induced necroptotic cell death in IEC-derived organoids could be markedly blocked by IL-20. Moreover, newly generatedStat2ΔIECmice, lacking STAT2 in IECs, were less susceptible to experimental colitis compared with wildtype controls and the administration of IL-20 suppressed colitis activity in wildtype animals.ConclusionIL-20 controls colitis and mucosal healing by interfering with the IFN/STAT2 death signalling pathway in IECs. These results indicate new directions for suppressing gut inflammation by modulating IL-20-controlled STAT2 signals.

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“…When eliminated by treatments or death during replication, E. coli release lipopolysaccharides (LPS) [ 7 ] that can activate the intestinal immune system and increase the expression of cytokines, such as IL-8, IL-10, IL-18, and TNF-α, by the intestinal epithelium under pathological conditions [ 8 ]. Consequently, structural and functional alterations in the intestine are presented, such as an increase in the paracellular transport of molecules, diarrhea, and mortality [ 9 ]. Due to the prohibition of antibiotics as growth promoters in poultry in some countries, multifactorial diseases have emerged, causing enteritis and intestinal disorders of unknown origin, leading to negative impacts on health and productive performance [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Gene expression of pro-inflammatory (IL-8, IL-18, TNF-α, and IFN-γ) and anti-inflammatory (IL-10) cytokines in the duodenum of broiler chickens exposed to lipopolysaccharides from Escherichia coli and Bacillus subtilis

2023

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Background and Aim: Intestinal infections are associated with Gram-negative bacteria like Escherichia coli. When eliminated by treatments during replication, E. coli release lipopolysaccharides (LPS) that can activate the intestinal immune system and increase the expression of cytokines, such as interleukin (IL)-8, IL-18, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), by the intestinal epithelium under pathological conditions. This study aimed to evaluate the addition of Bacillus subtilis to the duodenal gene expression of pro-inflammatory and anti-inflammatory cytokines in broilers exposed to LPS from E. coli. Materials and Methods: RNA was extracted using the Zymo Research total RNA commercial kit, according to the manufacturer's specifications, from the intestinal tissue of the duodenum previously resuspended in the lysis buffer of the kit. The expression of the cytokines of interest was measured using the QuantiNova SYBR green real-time polymerase chain reaction kit (Qiagen). Transcript quantification was performed by the ΔΔC(t) method using glyceraldehyde 3-phosphate dehydrogenase as a normalizing constitutive gene. Results: For the measurement of pro-inflammatory (IL-8, IL-18, TNF-α, and IFN-γ) and anti-inflammatory (IL-10) cytokines, there was no statistically significant difference (p > 0.05) between the basal diet and the diet with antibiotic (avilamycin). There was a statistical difference (p < 0.05) between diets with LPS. The diet with B. subtilis presented the lowest expression; the results differed on each sampling day (days 14, 28, and 42). Conclusion: A decrease in the expression of pro-inflammatory cytokines (IL-8, IL-18, TNF-α, and IFN-γ) and an increase in IL-10 (anti-inflammatory) was observed; in this way, a balance of the inflammatory response to bacterial infection is achieved, suggesting that the use of B. subtilis as an additive in a broiler diet has a similar effect to that produced with antibiotic growth promoter. Keywords: antibiotic, enteritis, Escherichia coli, lipopolysaccharides.

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Interferons at the crossroad of cell death pathways during gastrointestinal inflammation and infection

Cited by 7 publications

References 191 publications

Paneth cells as the cornerstones of intestinal and organismal health: a primer

Paneth cells as the cornerstones of intestinal and organismal health: a primer

IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling

Gene expression of pro-inflammatory (IL-8, IL-18, TNF-α, and IFN-γ) and anti-inflammatory (IL-10) cytokines in the duodenum of broiler chickens exposed to lipopolysaccharides from Escherichia coli and Bacillus subtilis

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