
Fulltext:
81781.pdf
Embargo:
until further notice
Size:
2.355Mb
Format:
PDF
Description:
publisher's version
Publication year
2009Source
Journal of Immunology, 183, 5, (2009), pp. 3383-9ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Rheumatology
Neurology
Internal Medicine
Journal title
Journal of Immunology
Volume
vol. 183
Issue
iss. 5
Page start
p. 3383
Page end
p. 9
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Infection and autoimmunityAbstract
Eicosanoids are essential mediators of the inflammatory response and contribute both to the initiation and the resolution of inflammation. Leukocyte-type 12/15-lipoxygenase (12/15-LO) represents a major enzyme involved in the generation of a subclass of eicosanoids, including the anti-inflammatory lipoxin A(4) (LXA(4)). Nevertheless, the impact of 12/15-LO on chronic inflammatory diseases such as arthritis has remained elusive. By using two experimental models of arthritis, the K/BxN serum-transfer and a TNF transgenic mouse model, we show that deletion of 12/15-LO leads to uncontrolled inflammation and tissue damage. Consistent with these findings, 12/15-LO-deficient mice showed enhanced inflammatory gene expression and decreased levels of LXA(4) within their inflamed synovia. In isolated macrophages, the addition of 12/15-LO-derived eicosanoids blocked both phosphorylation of p38MAPK and expression of a subset of proinflammatory genes. Conversely, 12/15-LO-deficient macrophages displayed significantly reduced levels of LXA(4), which correlated with increased activation of p38MAPK and an enhanced inflammatory gene expression after stimulation with TNF-alpha. Taken together, these results support an anti-inflammatory and tissue-protective role of 12/15-LO and its products during chronic inflammatory disorders such as arthritis.
This item appears in the following Collection(s)
- Academic publications [227900]
- Electronic publications [107389]
- Faculty of Medical Sciences [86236]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.