Dataset Information

Reynolds2006 - Reduced model of the acute inflammatory response

ABSTRACT: Angela Reynolds, Jonathan Rubin, Gilles Clermont, Judy Day, Yoram Vodovotz & G. Bard Ermentrout. A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation. Journal of Theoretical Biology 242, 1 (2006). The acute inflammatory response, triggered by a variety of biological or physical stresses on an organism, is a delicate system of checks and balances that, although aimed at promoting healing and restoring homeostasis, can result in undesired and occasionally lethal physiological responses. In this work, we derive a reduced conceptual model for the acute inflammatory response to infection, built up from consideration of direct interactions of fundamental effectors. We harness this model to explore the importance of dynamic anti-inflammation in promoting resolution of infection and homeostasis. Further, we offer a clinical correlation between model predictions and potential therapeutic interventions based on modulation of immunity by anti-inflammatory agents.

SUBMITTER: Sarubini Kananathan

PROVIDER: BIOMD0000000714 | BioModels | 2024-09-02

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	BIOMD0000000714?filename=AsepticDeath.cps	Other
	BIOMD0000000714?filename=AsepticDeath.sedml	Other
	BIOMD0000000714?filename=HealthyOutcome-biopax2.owl	Owl
	BIOMD0000000714?filename=HealthyOutcome-biopax3.owl	Owl
	BIOMD0000000714?filename=HealthyOutcome-matlab.m	Other

Items per page:

1 - 5 of 16

Publications

A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation.

Reynolds Angela A Rubin Jonathan J Clermont Gilles G Day Judy J Vodovotz Yoram Y Bard Ermentrout G G

Journal of theoretical biology 20060403 1

The acute inflammatory response, triggered by a variety of biological or physical stresses on an organism, is a delicate system of checks and balances that, although aimed at promoting healing and restoring homeostasis, can result in undesired and occasionally lethal physiological responses. In this work, we derive a reduced conceptual model for the acute inflammatory response to infection, built up from consideration of direct interactions of fundamental effectors. We harness this model to expl ...[more]

PMID: 16584750

Similar Datasets

Project description:The gene expression of murine splenic myeloid derived suppressor cells treated with Tff2 is characterized. The motivation of the study originates in the fact that Gr1+Cd11b+ myeloid-derived suppressor cells (MDSCs), which resemble immature myeloid cells (IMCs), expand during cancer in response to inflammatory cytokines and accumulate in the spleen. MDSCs promote neoplastic progression through their suppression of anti-tumourigenic cytotoxic T-cells. MDSCs are also rapidly expanded following acute insults, but in cancer as opposed to acute inflammation, MDSCs persist. It is now recognized that a vagally-mediated, anti-inflammatory reflex arc promoting acetylcholine secretion by Cd4+ (Cd44hiSelllo) T cells, is necessary for a return to homeostasis after an acute insult. Failure of this restorative neural circuit might contribute to unabated procarcinogenic inflammation, with the chronic expansion of MDSCs driving carcinogenesis. Trefoil factor 2 (Tff2) is a secreted anti-inflammatory peptide produced by both epithelial cells and a small subset of splenic T cell. In this study, we show that splenic Tff2 is induced in vagally-modulated memory T cells to suppress the expansion of MDSCs in response to chemical and carcinogenic injury. Deletion of Tff2 interrupts this anti-inflammatory neural arc and leads to expanded MDSCs and a dramatically increased incidence of colorectal cancer. Tff2 directly suppresses proliferation of myeloid progenitors, in a large part through upregulation of cell-bound Apolipoprotein E (ApoE), which has previously been shown to suppress proliferation of haematopoietic stem and progenitor cells. The predisposition to inflammation-associated cancer can be rescued through transgenic overexpression of splenic Tff2, adenoviral transfer of Tff2 expression or transplantation of Tff2-expressing haematopoietic cells. Thus, Tff2 production in memory T cells, is regulated by the vagus nerve, plays a central role in arresting procarcinogenic MDSC proliferation, and offers a novel approach to the prevention and treatment. A. Gr1+Cd11b+ splenic cells from Tff2-/- mice treated with Csf2 (n=4). B. Gr1+Cd11b+ splenic cells from Tff2-/- mice treated with Tff2 and Csf2 (n=4).