Synergistic hepatoprotective effect of the TLR5 agonist CBLB502 and its downstream effector IL-22
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE160465 | GEO | 2021/10/28
REPOSITORIES: GEO
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Project description:Synergistic hepatoprotective effect of the TLR5 agonist CBLB502 and its downstream effector IL-22
| PRJNA673242 | ENA
Project description:TLR5 agonist CBLB502 has been reported playing protective effects again IR, Here we find CBLB502 might protect cis-platin induced liver and kidney damages.
2023-08-01 | GSE210655 | GEO
Project description:Activators of innate immunity may have potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin (IL)-22, which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection, and thus holds promise as a broad-spectrum antiviral agent.
2014-11-30 | GSE62479 | GEO
Project description:Interleukin (IL) - 22 is a cytokine that plays a critical role in the maintenance of intestinal epithelial homeostasis. Its downstream functions are mediated through ligation of its heterodimeric receptor comprised of IL-22 receptor subunit alpha 1 (IL-22Ra1) and IL-10R2, and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and production of antimicrobials. Emerging studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (LacNAc) chains. Additionally, we show that IL-22 signaling regulates levels of the a1-3-fucosylated Lewis X (Lex) blood group antigen and this glycan epitope is primarily displayed on heavily O-glycosylated intestinal epithelial glycoproteins. The IL-22-mediated increase in Lex antigen levels requires B3GNT7, as disruption of B3GNT7 expression moderated the IL-22-dependent increase in Lex antigen levels. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, the data presented here identify B3GNT7 as a critical intermediary in IL-22-dependent induction of intestinal fucosylation of O-linked glycans and uncover a novel role for B3GNT7 in intestinal glycosylation.
2021-11-27 | GSE154889 | GEO
Project description:Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22-/- mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.
2017-02-03 | PXD005666 | Pride
Project description:Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. When compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.
2017-03-08 | GSE80419 | GEO
Project description: Not available
| S-EPMC8024273 | biostudies-literature
Project description:RNA-seq analysis of colon tissue from mice treated with PBS, WT IL-22, or engineered IL-22 variant 22-B3.
2021-10-26 | GSE160217 | GEO
Project description:Background and aims: Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6 type cytokine signaling required for hepatocyte proliferation and hepatoprotection but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. Methods: We investigated the role of Stat3 in inflammation-induced cholestatic liver injury and used mice lacking the multidrug resistance gene 2 (mdr2-/-) as a model for SC. Results: We demonstrate that conditional inactivation of stat3 in hepatocytes and cholangiocytes (stat3 delta hc) of mdr2-/- mice strongly aggravated bile acid-induced liver injury and fibrosis. A similar phenotype was observed in mdr2-/- mice lacking IL-6 production. Biochemical and molecular characterization suggested that Stat3 exerts hepatoprotective functions in both, hepatocytes and cholangiocytes. Loss of Stat3 in cholangiocytes led to increased expression of TNFα which might reduce the barrier function of bile ducts. Loss of Stat3 in hepatocytes led to upregulation of bile acid biosynthesis genes and downregulation of hepatoprotective epidermal growth factor receptor and insulin-like growth factor 1 signaling pathways. Consistently, stat3deltahc mice were more sensitive to cholic acid-induced liver damage than control mice. Conclusions: Our data suggest that Stat3 prevents cholestasis and liver damage in sclerosing cholangitis via regulation of pivotal functions in hepatocytes and cholangiocytes. Affymetrix microarray analyses was performed to identify metabolic and molecular pathways in stat3Dhc mdr2-/- mice that lead to cholestasis and bile acid-induced liver injury. To avoid false positive results that are due to differential cellular composition, we defined the onset of fibrosis and expression of fibrogenic factors in stat3Dhc mdr2-/- mice.
2010-10-20 | E-GEOD-18759 | biostudies-arrayexpress
Project description:Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disorder that primarily affects premature infants. Despite decades of research, this disease remains a significant cause of death in the absence of efficient therapeutics. Interleukin (IL)-22 has been shown to play a critical role in maintaining the gut barrier, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models with an established microbiome. However, the importance of IL-22 signaling in the regulation of gut homeostasis and protection in neonates that lack an established microbiome remains unknown. Therefore, the aim of the current study is to investigate the role of IL-22 in the neonatal intestinal epithelium under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning. In addition, both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or mice lacking the expression of IL-22 receptor in intestinal epithelial cells, display a similar susceptibility of neonates to NEC consistent with the lack of endogenous IL-22 at this critical stage of intestinal development. Conversely, treatment with recombinant IL-22 during NEC substantially reduces disease severity. This IL-22-mediated protection is associated with enhanced epithelial regeneration and increased expression of several antimicrobial genes. Strikingly, despite an IL-22-mediated induction of an antimicrobial transcriptional program, the composition of the intestinal microbial communities remains unchanged. Taken together, this study demonstrates that an IL-22 signaling axis promotes protection against neonatal NEC through the induction of epithelial cell regeneration.
2021-05-18 | GSE155172 | GEO