12/15-Lipoxygenase counteracts inflammation and tissue damage in arthritis

Krönke G, Katzenbeisser J, Uderhardt S, Zaiss M, Scholtysek C, Schabbauer G, Zarbock A, Koenders MI, Axmann R, Zwerina J, Baenckler HW, Van Den Berg W, Voll RE, Kuehn H, Joosten LAB, Schett G (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Book Volume: 183

Pages Range: 3383-3389

Journal Issue: 5

DOI: 10.4049/jimmunol.0900327

Abstract

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 A4 (LXA4). 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 LXA4 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 LXA4, which correlated with increased activation of p38MAPK and an enhanced inflammatory gene expression after stimulation with TNF-α. 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. Copyright © 2009 by The American Association of Immunologists, Inc.

Authors with CRIS profile

Involved external institutions

Humboldt-Universität zu Berlin Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Radboud University Nijmegen Netherlands (NL) Medizinische Universität Wien Austria (AT)

How to cite

APA:

Krönke, G., Katzenbeisser, J., Uderhardt, S., Zaiss, M., Scholtysek, C., Schabbauer, G.,... Schett, G. (2009). 12/15-Lipoxygenase counteracts inflammation and tissue damage in arthritis. Journal of Immunology, 183(5), 3383-3389. https://doi.org/10.4049/jimmunol.0900327

MLA:

Krönke, Gerhard, et al. "12/15-Lipoxygenase counteracts inflammation and tissue damage in arthritis." Journal of Immunology 183.5 (2009): 3383-3389.

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