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Collagen induced arthritis in dba/1j mice associates with oxylipin changes in plasma

ABSTRACT: Oxylipins play important roles in various biological processes and are considered as mediators of inflammation for a wide range of diseases such as rheumatoid arthritis (RA). The purpose of this research was to study differences in oxylipin levels between a widely used collagen-induced arthritis (CIA) mice model and healthy control (Ctrl) mice. DBA/1J male mice (age: 6-7 weeks) were selected and randomly divided into two groups, viz. a CIA- and a Ctrl group. The CIA mice were injected intraperitoneal (i.p.) with the joint cartilage component collagen type II (CII) and an adjuvant injection of lipopolysaccharide (LPS). Oxylipin metabolites were extracted from plasma for each individual sample using solid phase extraction (SPE) and were detected with high performance liquid chromatography/tandem mass spectrometry (HPLC-ESI-MS/MS), using dynamic multiple reaction monitoring (dMRM). Both univariate and multivariate statistical analysis was applied. The results in univariate student's t-test revealed 10 significantly up- or down-regulated oxylipins in CIA mice, which were supplemented by another 6 additional oxylipins, contributing to group clustering upon multivariate analysis. The dysregulation of these oxylipins revealed the presence of ROS-generated oxylipins and an increase of inflammation in CIA mice. The results also suggested that the Collagen-induced arthritis might associate with dysregulation of apoptosis, possibly inhibited by activated NF- κ B because of insufficient PPAR-γ ligands.

INSTRUMENT(S): 6490 Triple Quadrupole LC/MS (Agilent)

SUBMITTER: Michael van Vliet

PROVIDER: MTBLS243 | MetaboLights | 2015-11-04

REPOSITORIES: MetaboLights

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Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments. This model is hosted on BioModels Database and identified by: BIOMD0000000550. 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.

Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis - Age Dependant This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments. This model is hosted on BioModels Database and identified by: BIOMD0000000549. 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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Collagen induced arthritis in dba/1j mice associates with oxylipin changes in plasma

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