Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase

Daniel DiMeo; Jun Tian; Juan Zhang; Seiko Narushima; Daniel J Berg

doi:10.1111/j.1365-2567.2007.02694.x

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Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase

Journal article

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Peer reviewed

Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase

Daniel DiMeo, Jun Tian, Juan Zhang, Seiko Narushima and Daniel J Berg

Immunology, Vol.123(2), pp.250-262

02/2008

DOI: 10.1111/j.1365-2567.2007.02694.x

PMCID: PMC2433306

PMID: 17894798

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Abstract

Eicosanoids (prostaglandins and leukotrienes) are important mediators of inflammatory responses. These lipid mediators may also regulate the production of peptide mediators of the immune system. In this study, we investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on interleukin (IL)-10 production. IL-10 is a key regulator of immune and inflammatory responses, and previous studies have suggested that prostaglandins effect their immunosuppressive functions in part by stimulation of IL-10 production. We therefore investigated whether leukotriene production would have a similar role in regulation of IL-10 production. We have made the striking observation that absence of 5-LO-derived leukotrienes results in increased IL-10 production with a concomitant decrease in the production of pro-inflammatory cytokines, including tumour necrosis factor (TNF)-alpha and IL-12. Moreover, T-cell cytokine production in the absence of 5-LO-derived leukotrienes results in increased IL-4 production and decreased interferon (IFN)-gamma production. This may be in part secondary to increased IL-10 production and its effects on dendritic cell function resulting in altered T-cell differentiation. These findings indicate that, in addition to the central role leukotrienes play in the acute inflammatory response, endogenous leukotrienes are also important regulators of inflammatory cytokine production, via regulation of IL-10 production and in vivo differentiation of T cells.

Immunization

Oligodeoxyribonucleotides - immunology

Spleen - immunology

Dendritic Cells - immunology

Cells, Cultured

Th2 Cells - immunology

Arachidonate 5-Lipoxygenase - deficiency

Leukotriene B4 - immunology

Lipopolysaccharides - immunology

Arachidonate 5-Lipoxygenase - immunology

Mice, Knockout

CD4-Positive T-Lymphocytes - immunology

Animals

Inflammation Mediators - metabolism

Interleukin-10 - biosynthesis

Mice

Cytokines - biosynthesis

Details

Title: Subtitle: Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase
Creators: Daniel DiMeo - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA, USA
Jun Tian
Juan Zhang
Seiko Narushima
Daniel J Berg
Resource Type: Journal article
Publication Details: Immunology, Vol.123(2), pp.250-262
DOI: 10.1111/j.1365-2567.2007.02694.x
PMID: 17894798
PMCID: PMC2433306
NLM abbreviation: Immunology
ISSN: 0019-2805
eISSN: 1365-2567
Grant note: R01 DK 060718-01A2 / NIDDK NIH HHS R01 DK060718 / NIDDK NIH HHS
Language: English
Date published: 02/2008
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094346502771

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