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Collagen Induced Arthritis in DBA/1J Mice Associates with Oxylipin Changes in Plasma

Author: He, M. · Wijk, E. van · Berger, R. · Wang, M. · Strassburg, K. · Schoeman, J.C. · Vreeken, R.J. · Wietmarschen, H. van · Harms, A.C. · Kobayashi, M. · Hankemeier, T. · Greef, J. van der
Source:Mediators of Inflammation, 2015
Identifier: 529706
doi: doi:10.1155/2015/543541
Article number: 543541
Keywords: Biology · Collagen type 2 · Lipopolysaccharide · Oxylipin · Animal experiment · Animal model · Arthritis · Articular cartilage · Controlled study · Electrospray mass spectrometry · High performance liquid chromatography · Male · Mouse · Nonhuman · Oxidative stress · Tandem mass spectrometry · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · ELSS - Earth, Life and Social Sciences


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, namely, a CIA and a Ctrl group. The CIA mice were injected intraperitoneally (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 analyses were applied. The results in univariate Student's t-test revealed 10 significantly up- or downregulated 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-B because of insufficient PPAR-γ ligands. © 2015 Min He et al.