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ID 119545
Author
Hakoi, Haruka Tokushima University
Miki, Yoshimi Tokushima University|The University of Tokyo
Nomura, Saki Tokushima University
Nakajima, Kimiko Kochi University
Terashima-Murase, Chiaki Nagoya University
Takeichi, Takuya Nagoya University
Sano, Shigetoshi Kochi University
Akiyama, Masashi Nagoya University
Sakasegawa, Shin-ichi National Institute of Advanced Industrial Science and Technology|Asahi Kasei Pharma Corporation
Murakami, Makoto The University of Tokyo|Japan Agency for Medical Research and Development
Yamamoto, Kei Tokushima University|Japan Agency for Medical Research and Development Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
Group IIF phospholipase A2
Lysoplasmalogen
Thermocrispum lysophospholipase D
Psoriasis
Lipidomics
Content Type
Journal Article
Description
Epidermal lipids play important roles in skin homeostasis and diseases. Psoriasis is an inflammatory disease characterized by keratinocyte hyperproliferation and Th17 immune responses. We previously reported that ethanolamine-type lysoplasmalogen (P-LPE), preferentially produced by group IIF secreted PLA2 (sPLA2-IIF/PLA2G2F) that is expressed in the suprabasal epidermis, promotes epidermal hyperplasia in psoriatic inflammation. Herein, we show that forcible degradation of epidermal P-LPE by topical application of recombinant lysophospholipase D (LyPls-PLD) from Thermocrispum, a lysoplasmalogen-specific hydrolase, attenuated epidermal hyperplasia and inflammation in imiquimod-induced and K5.Stat3C-transgenic mouse psoriasis models. In humans, P-LPE levels were elevated in the tape-stripped stratum corneum of patients with psoriasis. Moreover, in primary cultured human epidermal keratinocytes, aberrant cell proliferation and activation by psoriatic cytokines were sPLA2-IIF/P-LPE-dependent and were suppressed by the addition of LyPls-PLD with a decrease in P-LPE. These findings confirm that the sPLA2-IIF/P-LPE axis in the epidermis indeed regulates psoriasis, that P-LPE is a lipid biomarker that predicts the severity of psoriasis, and that pharmacological removal of this bioactive lipid is useful to prevent the disease. Thus, our study may lead to the development of drug discovery and diagnostic techniques based on this pathway.
Journal Title
Biochimie
ISSN
16386183
03009084
NCID
AA11522535
AA00564792
Publisher
Elsevier|Société Française de Biochimie et Biologie Moléculaire (SFBBM)
Volume
215
Start Page
75
End Page
87
Published Date
2023-10-04
Rights
© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
https://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Bioscience and Bioindustry