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Time-course gene expression profiles of the synovial tissues in collagen-induced arthritis

ABSTRACT: We observed resolution of inflammatory response in collagen-induced arthritis (CIA) mice. To identify molecular signatures defining resolution of the CIA, we applied microarray analysis for synovial tissues in the CIA mice in 6 (induction), 9 (peak) and 15 weeks (resolution) after immunization. To identify genes related to CIA resolution, we performed the following comparisons of gene expression profiles: peak versus induction phase and resolution versus peak phase. We identified that three genes, Itgb1, Ywhaz and Rps3, are the key regulators for the resolution by measuring degree, betweenness and closeness centrality in reconstructed network based on protein-protein interaction data. To confirm this result, we compared the gene and protein expression level of the three regulators between the two phases of inflammation. Furthermore, we showed that the gene and protein expression level of the three regulators are up-regulated in regulatory T cells and type 2 macrophages than other subtypes of CD4+ T cells and macrophages, and also we examined that recombinant peritoneal macrophages of the three regulators can modulate the expression of pro-inflammatory and anti-inflammatory cytokines. Thus, our findings suggest that those regulators can be employed as therapeutic uses for resolving inflammation

ORGANISM(S): Mus musculus

PROVIDER: GSE99087 | GEO | 2020/05/19

REPOSITORIES: GEO

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Project description:Dunster2014 - WBC Interactions (Model1) This is a sub-model of a three-step inflammatory response modelling study. The model includes distinct populations of white blood cells namely, macrophages and active and apoptotic neutrophil populations. Neutrophil apoptosis rate is predicted to be crucial for the qualitative nature of the system. This model is described in the article: The resolution of inflammation: a mathematical model of neutrophil and macrophage interactions. Dunster JL, Byrne HM, King JR. Bull. Math. Biol. 2014 Aug; 76(8): 1953-1980 Abstract: There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer's disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis. This model is hosted on BioModels Database and identified by: BIOMD0000000616. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Time-course gene expression profiles of the synovial tissues in collagen-induced arthritis

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