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ID 119239
Title Alternative
sPLA2- IID, an Immunosuppressive sPLA2
Author
Miki, Yoshimi Tokyo Metropolitan Institute of Medical Science
Kidoguchi, Yuh Tokyo Metropolitan Institute of Medical Science|Tokyo Denki University
Sato, Mariko Tokyo Metropolitan Institute of Medical Science|Tokyo Denki University
Taketomi, Yoshitaka Tokyo Metropolitan Institute of Medical Science
Taya, Choji Tokyo Metropolitan Institute of Medical Science
Muramatsu, Kazuaki Tokyo Denki University
Gelb, Michael H. University of Washington
Yamamoto, Kei Tokyo Metropolitan Institute of Medical Science|Tokushima University|Japan Agency for Medical Research and Development Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Murakami, Makoto Tokyo Metropolitan Institute of Medical Science|Japan Agency for Medical Research and Development
Content Type
Journal Article
Description
Phospholipase A2 enzymes have long been implicated in the promotion of inflammation by mobilizing pro-inflammatory lipid mediators, yet recent evidence suggests that they also contribute to anti-inflammatory or pro-resolving programs. Group IID-secreted phospholipase A2 (sPLA2-IID) is abundantly expressed in dendritic cells in lymphoid tissues and resolves the Th1 immune response by controlling the steady-state levels of anti-inflammatory lipids such as docosahexaenoic acid and its metabolites. Here, we show that psoriasis and contact dermatitis were exacerbated in Pla2g2d-null mice, whereas they were ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice. These phenotypes were associated with concomitant alterations in the tissue levels of ω3 polyunsaturated fatty acid (PUFA) metabolites, which had the capacity to reduce the expression of pro-inflammatory and Th1/Th17- type cytokines in dendritic cells or lymph node cells. In the context of cancer, however, Pla2g2d deficiency resulted in marked attenuation of skin carcinogenesis, likely because of the augmented anti-tumor immunity. Altogether, these results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.
Journal Title
Journal of Biological Chemistry
ISSN
00219258
1083351X
NCID
AA1202441X
Publisher
American Society for Biochemistry and Molecular Biology|Elsevier
Volume
291
Issue
30
Start Page
15588
End Page
15601
Published Date
2016-05-21
Rights
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Bioscience and Bioindustry