Impact of mPGES-1 on the resolution of zymosan-induced peritonitis in mice
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ABSTRACT:
PROVIDER: PRJNA690115 | ENA |
REPOSITORIES: ENA
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Project description:Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E2 (PGE2), are well characterized mediators of inflammation. PGE2 is produced in an inducible manner in macrophages (Mf) by microsomal PGE2-synthase-1 (mPGES-1), with the notion that it also conveys pro-resolving properties. We aimed to characterize the role of mPGES-1 during resolution of acute, zymosan-induced peritonitis. Experimentally, we applied the mPGES-1 inhibitor compound III (CIII) once the inflammatory response was established and confirmed its potent PGE2-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and Mf during the resolution process. mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating Mf upon mPGES-1 inhibition. Besides elevated Cx3cr1 expression, its ligand CX3CL1 was enriched in the peritoneal lavage of the mice, produced by epithelial cells upon mPGES-1 inhibition. CX3CL1 not only increased adhesion and survival of Mf, but its neutralization also completely reversed elevated inflammatory cell numbers, thereby normalizing the cellular, peritoneal composition during resolution. Our data suggest that mPGES-1-derived PGE2 contributes to resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury.
2021-02-10 | GSE164364 | GEO
Project description:CARD9 is an adapter protein, which plays a critical role in anti-fungal immunity. However, the role of CARD9 in fungal-induced autophagy remains unknown. In this study, we demonstrated that Card9-/- mice displayed more severe phenotype of zymosan-induced peritonitis, presenting as multiple organs injury and increased systemic inflammation. Moreover, the number of macrophage in spleen was increased in Card9-/- mice. Further studies revealed that autophagy was impaired in peritoneal macrophages of Card9-/- -peritonitis mice. Notably, the autophagy agonist, rapamycin, ameliorated peritonitis in Card9-/- mice. Moreover, Card9 mediates the interaction of Malt1 and P62 upon zymosan stimulation. Together, our results confirmed the protective role of Card9 in the development of peritonitis via regulates autophagy in macrophage cells. The study indicates Card9 may be a potential therapeutic target for peritonitis.
2024-01-01 | GSE164572 | GEO
Project description:Nanostring analysis of macrophage subsets following zymosan-induced peritonitis
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Project description:Total RNA was extracted from monocyte and macrophages isolated from the peritoneal cavity of un-inflamed mice or 4, 24, 48 an 72h after mice had been injected with 0.1 or 10mg zymosan
2011-07-30 | E-MEXP-3189 | biostudies-arrayexpress
Project description:TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production. In this dataset, expression data of genes induced by septic peritonitis in spleens from TLR-deficient and wildtype mice are included. 3 groups (septic TLR-deficient mice, septic wildtype mice, and untreated wildtype mice) with 4 replicates each.
2011-06-27 | E-GEOD-24327 | biostudies-arrayexpress
Project description:Resident macrophages from naïve mice or resident/inflammatory macrophages from mice treated with zymosan(10ug) 3 days prior were purified from C57BL/6 CD45.2+ donor mice. Purified populations were transferred into mirroring CD45.1/2+ recipient mice or clodronate pre-treated recipient mice. Donor populations were purified 8 weeks following transfer for Nanostring analysis.
2021-01-28 | GSE165036 | GEO
Project description:TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production.
2011-06-28 | GSE24327 | GEO
Project description:In our previous work we substantiated the ability of the Fgd5-mCherry mice to tag hematopoietic stem cells (HSCs) during immune response (Bujanover et al., 2018). While most of the research is focused on viral-bacterial models mediated by a Th1 response less has been investigated on Th2 mediated hypersensitivity. Our current experimental model of allergic peritonitis seeks to understand the effect of a Th2 mediated immune response utilizing our transgenic Fgd5-mCherry mice. Our results showed no significant change in quantity of HSCs and their immediate progenitors in the bone-marrow post treatment. Furthermore, transplant experiments showed no significant change in the long term multipotent ability of HSCs vs. control. Examining the cell cycle state of HSCs, quiescence is an essential property for stemness, we find no evidence of proliferation. We continued to sort and bulk RNAseq HSCs after allergic peritonitis showing relatively small changes in expression profile. Taken together, this data suggests no prominent response of HSCs to our Th2-mediated hypersensitivity model.
2020-04-30 | GSE133282 | GEO
Project description:Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Tolllike receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-b synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-b was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-b, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.
2021-01-27 | GSE165523 | GEO
Project description:Peritonitis and subsequent sepsis lead to high morbidity and mortality in response to uncontrolled systemic inflammation primarily mediated by macrophages. We investigated whether the administration of a natural biosynthetic precursor of NAD+, β-nicotinamide mononucleotide (β‐NMN), could prevent clinical deterioration effects of sepsis. To this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate (TGC) to induce a sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity. β-NMN was administered for 4 days after CLP and for 3 days post TGC treatment. Administration of β‐NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis. Transcriptomic analysis of hearts and lungs 24 hours post CLP-induction, revealed that β-NMN downregulated genes controlling immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria biogenesis, and autophagy. In the thioglycolate model, β‐NMN treatment significantly reduced phagolysosomes acidification and inflammatory mediators secretion from bacteria-stimulated peritoneal macrophages. Transcriptomic signature of these macrophages showed that β‐NMN administration limited the pro-inflammatory M1 phenotype, induced the expression of specific markers of M2 type macrophages and significantly impacted gens involved in NAD+ metabolism.
2022-06-08 | GSE199156 | GEO