Chapter 17 Zymosan‐Induced Peritonitis as a Simple Experimental System for the Study of Inflammation

Cash, Jenna L.; White, Gemma E.; Greaves, David R.

doi:10.1016/s0076-6879(09)05417-2

Cited by 114 publications

(114 citation statements)

References 45 publications

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“…To determine whether LXR-NPs are anti-inflammatory and pro resolving in vivo , we used a standard zymosan-induced peritonitis model [24] to quantitatively assess the resolution of inflammation in wild-type C57BL/6 mice. The mice were intravenously (i.v.)…”

Section: Resultsmentioning

confidence: 99%

Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation

Gadde

Even-Or

Kamaly

et al. 2014

Adv Healthcare Materials

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Liver X receptors (LXRs) attenuate inflammation by modulating the expression of key inflammatory genes, making LXRs and their ligands particularly attractive candidates for therapeutic intervention in cardiovascular, metabolic, and/or inflammatory diseases. In this study, we demonstrate enhanced proresolving activity of nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs), developed from a combinatorial library of more than 70 formulations with variations in critical physicochemical parameters. The library of LXR-NPs was engineered via self-assembly of biodegradable poly(lactide)- and poly(lactide-co-glycolide)-based polymers. In vitro studies on peritoneal macrophages confirmed that LXR-NPs were significantly more effective than the free agonist (GW3965) at downregulating pro-inflammatory mediators (MCP-1 and TNFα), as well as inducing the expression of LXR target genes (ABCA1 and SREBP1c). Through a zymosan-induced acute peritonitis in vivo model, LXR-NPs were found to be more efficient than free LXR agonist at limiting the recruitment of polymononuclear neutrophils (50% vs. 17%) and at decreasing the resolution interval up to 4 h. In addition, treatment with LXR-NPs significantly suppressed gene expression and secretion of pro-inflammatory factors MCP-1 and TNFα in peritoneal macrophages when compared to LXR agonist alone. Furthermore, the LXR-NPs suppressed secretion of these pro-inflammatory factors by monocytes and macrophages more efficiently than the commercial drug dexamethasone. Overall, these findings demonstrate that LXR-NPs are capable of promoting resolution of inflammation and highlight the prospect of LXR-based nanotherapeutics for inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation

Gadde

Even-Or

Kamaly

et al. 2014

Adv Healthcare Materials

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“…However, at a later phase, COX-2 promoted resolution by generating an alternate set of reportedly anti-inflammatory prostaglandins [i.e., PGD 2 and its dual dehydration end-product, 15-deoxy-D 12,14 -PGJ 2 (15d-PGJ 2 )] through a process now regarded as ''eicosanoid class switching''. As an extension of this work, Rajakariar et al used the murine model of zymozan-induced peritonitis (commonly used to study acute inflammation and inflammatory resolution [22]) to demonstrate that inflammation in PGDS knockout mice was more severe and of quicker onset relative to wild-type littermates [23]. Most importantly, the inflammatory response in PGDS-deficient mice failed to resolve in a timely fashion.…”

Section: Introductionmentioning

confidence: 89%

The cardinal role of the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis

Mancini

Battista

2011

Inflamm. Res.

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The process of inflammation is regulated in part by bioactive lipids of which prostaglandins/eicosanoids form an important class. We provide evidence that the phospholipase A(2)/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E(2) (PCPP) axis is positioned at the core of a natural regulatory circuit controlling the initiation, magnitude, duration, and resolution of the inflammatory response. During the inflammatory phase, proinflammatory cytokine, chemokine and matrix destructive metalloprotease expression levels are moderated by the PCPP axis through the modulation of signaling pathways that control proinflammatory gene expression at transcriptional, post-transcriptional, and translational levels. The PCPP axis also contributes to the activation of lipid mediator class switching; this highly coordinated process results in the biosynthesis of lipoxins and resolvins that promote inflammatory resolution through a variety of cellular and molecular mechanisms. The PCPP axis activity is autoregulated by way of a positive feedback circuit involving PGE(2)-mediated, p38 MAPK-dependent stabilization of COX-2 mRNA and COX-2 catalytic potentiation via its limited proteolytic cleavage (e.g., Ca(2+)-activated calpains). In conclusion, through its fine temporal modulation of multiple signaling cassettes via EP1-EP4 GPCRs, PGE(2) influences the onset, course, magnitude, and duration of the inflammatory response and functions as a key feedback regulator of the cellular and molecular processes controlling inflammation.

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“…26 After 48 hours, mice were euthanized and peritoneal lavage was performed. The recovered cells were stained for extracellular CD11b and F4/80 prior to fixation and permeabilization.…”

Section: Sterile Inflammationmentioning

confidence: 99%

NBS1 is required for macrophage homeostasis and functional activity in mice

Pereira-Lopes

Tur

Calatayud-Subias

et al. 2015

Blood

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• Nbs1 is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response.• In mice with a hypomorphic allele of Nbs1, macrophages exhibit increased senescence and abnormal proliferation and inflammatory responses. , macrophage activation-induced ROS caused increased levels of DNA damage that were associated with defects in proliferation, delayed differentiation, and increased senescence. Furthermore, upon stimulation, Nbs1 ΔB/ΔB macrophages exhibited increased expression of proinflammatory cytokines. In the in vivo 2,4-dinitrofluorobenezene model of inflammation, Nbs1 ΔB/ΔB animals showed increased weight and ear thickness. By using the sterile inflammation by zymosan injection, we found that macrophage proliferation was drastically decreased in the peritoneal cavity of Nbs1 ΔB/ΔB mice. Our findings show that NBS1 is crucial for macrophage function during normal aging. These results have implications for understanding the immune defects observed in patients with NBS and related disorders. (Blood. 2015;126(22):2502-2510

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Chapter 17 Zymosan‐Induced Peritonitis as a Simple Experimental System for the Study of Inflammation

Cited by 114 publications

References 45 publications

Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation

Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation

The cardinal role of the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis

NBS1 is required for macrophage homeostasis and functional activity in mice

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