Anti-inflammatory role of 15-lipoxygenase contributes to the maintenance of skin integrity in mice

Sang Nam Kim; Seun Akindehin; Hyun Jung Kwon; Yeon Ho Son; Abhirup Saha; Young Suk Jung; Je Kyung Seong; Kyung Min Lim; Jong Hyuk Sung; Krishna Rao Maddipati; Yun Hee Lee

doi:10.1038/s41598-018-27221-7

Anti-inflammatory role of 15-lipoxygenase contributes to the maintenance of skin integrity in mice

Sang Nam Kim, Seun Akindehin, Hyun Jung Kwon, Yeon Ho Son, Abhirup Saha, Young Suk Jung, Je Kyung Seong, Kyung Min Lim, Jong Hyuk Sung, Krishna Rao Maddipati, Yun Hee Lee

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

15-lipoxygenase is involved in the generation of specialized pro-resolving lipid mediators that play essential roles in resolution and inflammatory responses. Here, we investigated anti-inflammatory role of Alox15 in skin homeostasis. We demonstrated that knockout (KO) of Alox15 led to hair loss and disrupted the structural integrity of the dorsal skin. Alox15 KO resulted in loss of hair follicle stem cells and abnormal transition of dermal adipocytes into fibroblasts. Alox15 deficiency increased infiltration of proinflammatory macrophages and upregulated proinflammatory and necroptotic signaling in dermal adipose tissue in the dorsal skin. Lipidomic analysis revealed severe loss of resolvin D2 in the dorsal skin of Alox15 KO mice compared to wild type controls. Treatment with resolvin D2 reduced skin inflammation in Alox15 KO mice. Collectively, these results indicate that Alox15-mediated production of resolvin D2 is required to maintain skin integrity by suppressing dermal inflammation.

Original language	English
Article number	8856
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-27221-7
Publication status	Published - 2018 Dec 1

Bibliographical note

Funding Information:
We thank Dr. JG Granneman for discussions and comments on the manuscripts. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A6A3A04056472 (Y.H.L.)) and the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIP&MOHW) (No. NRF-2016M3A9D5A01953818 (Y.H.L.))

Publisher Copyright:
© 2018 The Author(s).

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abstract = "15-lipoxygenase is involved in the generation of specialized pro-resolving lipid mediators that play essential roles in resolution and inflammatory responses. Here, we investigated anti-inflammatory role of Alox15 in skin homeostasis. We demonstrated that knockout (KO) of Alox15 led to hair loss and disrupted the structural integrity of the dorsal skin. Alox15 KO resulted in loss of hair follicle stem cells and abnormal transition of dermal adipocytes into fibroblasts. Alox15 deficiency increased infiltration of proinflammatory macrophages and upregulated proinflammatory and necroptotic signaling in dermal adipose tissue in the dorsal skin. Lipidomic analysis revealed severe loss of resolvin D2 in the dorsal skin of Alox15 KO mice compared to wild type controls. Treatment with resolvin D2 reduced skin inflammation in Alox15 KO mice. Collectively, these results indicate that Alox15-mediated production of resolvin D2 is required to maintain skin integrity by suppressing dermal inflammation.",

author = "Kim, {Sang Nam} and Seun Akindehin and Kwon, {Hyun Jung} and Son, {Yeon Ho} and Abhirup Saha and Jung, {Young Suk} and Seong, {Je Kyung} and Lim, {Kyung Min} and Sung, {Jong Hyuk} and Maddipati, {Krishna Rao} and Lee, {Yun Hee}",

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AU - Saha, Abhirup

AU - Jung, Young Suk

AU - Seong, Je Kyung

AU - Lim, Kyung Min

AU - Sung, Jong Hyuk

AU - Maddipati, Krishna Rao

AU - Lee, Yun Hee

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N2 - 15-lipoxygenase is involved in the generation of specialized pro-resolving lipid mediators that play essential roles in resolution and inflammatory responses. Here, we investigated anti-inflammatory role of Alox15 in skin homeostasis. We demonstrated that knockout (KO) of Alox15 led to hair loss and disrupted the structural integrity of the dorsal skin. Alox15 KO resulted in loss of hair follicle stem cells and abnormal transition of dermal adipocytes into fibroblasts. Alox15 deficiency increased infiltration of proinflammatory macrophages and upregulated proinflammatory and necroptotic signaling in dermal adipose tissue in the dorsal skin. Lipidomic analysis revealed severe loss of resolvin D2 in the dorsal skin of Alox15 KO mice compared to wild type controls. Treatment with resolvin D2 reduced skin inflammation in Alox15 KO mice. Collectively, these results indicate that Alox15-mediated production of resolvin D2 is required to maintain skin integrity by suppressing dermal inflammation.

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Anti-inflammatory role of 15-lipoxygenase contributes to the maintenance of skin integrity in mice

Abstract

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