Analyses of lipid network using inflammatory dermatoses model mice

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: YAMAMOTO Kei 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (30304504)
• Project Period (FY): 2011 – 2013
• Keywords: 脂質代謝 / 脂質メディエーター / 皮膚疾患 / 接触性皮膚炎 / ホスホリパーゼＡ２ / 炎症収束

Research Abstract

Epidermal lipids play important roles in skin barrier and pathophysiological function. Although perturbed lipid metabolism often leads to skin abnormality, molecular mechanisms underlying this process still remain incompletely understood. In this research, we show that secreted PLA2 group IID (PLA2G2D) is preferentially expressed in dendritic cells (DCs) and displays a pro-resolving function. In hapten-induced contact dermatitis, resolution of inflammation was compromised in skin and LNs of PLA2G2D-deficient mice, in which the immune balance was shifted toward a proinflammatory state over an anti-inflammatory state. PLA2G2D in the LNs contributed to mobilization of a pool of DHA that could serve as precursors for pro-resolving lipid mediators such as resolvin D1. Our results highlight PLA2G2D as a"resolving sPLA2" that ameliorates inflammation through mobilizing pro-resolving lipid mediators and points to a potential use of this enzyme for treatment of inflammatory disorders.

Research Products

• [Journal Article] Lymphoid tissue phospholipase A_2 group IID resolves contact hypersensitivity by driving anti-inflammatory lipid mediators (2013)
  • Author(s): Miki, Y., Yamamoto, K., Taketomi, Y., Sato, H., Shimo, K., Kobayashi, T., Ishikawa, Y., Ishii, T., Nakanishi, H., Ikeda, K., Taguchi, R., Kabashima, K., Arita, M., Arai, H., Lambeau, G., Bollinger, J.M., Hara, S., Gelb, M.H., and Murakami, M.
  • Journal Title: J. Exp. Med. Volume: 210 Pages: 1217-1234
  • Peer Reviewed
• [Journal Article] Mast cell maturation is driven via a group III phospholipase A_2-prostaglandin D_2-DP1 receptor paracrine axis (2013)
  • Author(s): Taketomi, Y., Ueno, N., Kojima, T., Satom H., Murase, R., Yamamoto, K., Tanaka, S., Sakanaka, M., Nakamura, Nishito, Y., Kawana, M., Kambe, N., Ikeda, K., Taguchi, R., Nakamizo, S., Kabashima, K., Gelb, M.H., Arita, M., Yokomizo, T., Nakamura, M., Watanabe, K., Hirai, H., Nakamura, M., Okayama, Y., Ra, C., Aritake, K., Urade, Y., Morimoto, K., Sugimoto, Y., Shimizu, T., Narumiya, S., Hara, S., and Murakami, M.
  • Journal Title: Nat. Immunol. Volume: 14 Pages: 554-563
  • Peer Reviewed
• [Journal Article] 疾病における脂質代謝ネットワークの機能 (2013)
  • Author(s): 三木寿美、山本圭、村上誠
  • Journal Title: オレオサイエンス Volume: 13(10) Pages: 23-29
  • Peer Reviewed
• [Journal Article] The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity
  • Author(s): Sato, H., Taketomi, Y., Ushida, A., Isogai, Y., Kojima, T., Hirabayashi, T., Miki, Y., Yamamoto, K., Nishito, Y., Kobayashi, T., Ikeda, K., Taguchi, R., Hara, S., Ida, S., Miyamoto, Y., Watanabe, M., Baba, H., Miyata, K., Oike, Y., Gelb, M.H., and Murakami, M.
  • Journal Title: Cell Metabolism Volume: (in press) Pages: 2014
  • Peer Reviewed
• [Presentation] Epidermal phospholipase A_2 group IIF regulates keratinocyte differentiation and skin barrier through driving a unique set of lipid products (2013)
  • Author(s): Yamamoto, K., Miki, Y., Sato, M., Taketomi, Y., Gelb, M.H., Lambeau, G, and Murakami, M.
  • Organizer: 16th GEM/10th GERLI meeting 2013 GEM/GERLI Lipidomics meeting
  • Place of Presentation: Nice, France
  • Year and Date: 20131110-14
• [Presentation] Epidermal phospholipase A_2 group IIF regulates keratinocyte differentiation and skin barrier through driving a unique set of lipid products (2013)
  • Author(s): Yamamoto, K., Miki, Y., Sato, M., Taketomi, Y., Gelb, M.H., Lambeau, G, and Murakami, M.
  • Organizer: 13^<th> International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: San Juan, Puerto Rico
  • Year and Date: 20131103-06
• [Presentation] IIF型分泌性ホスホリパーゼA_2は皮膚疾患の進行に寄与する (2013)
  • Author(s): 山本圭、三木寿美、佐藤真利子、椛島健治、石川由起雄、石井壽晴、村上誠
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 20130911-13
• [Presentation] IIF型分泌性ホスホリパーゼA_2は表皮の恒常性維持および病態に寄与する (2013)
  • Author(s): 山本圭、三木寿美、佐藤真利子、武富芳隆、池田和貴、中西広樹、田口良、村上誠
  • Organizer: 第55回日本脂質生化学会
  • Place of Presentation: 宮城県松島町
  • Year and Date: 20130606-07
• [Presentation] GROUP IIF PHOSPHOLIPASE A_2 MAINTAINS SKIN HOMEOSTASIS (2013)
  • Author(s): Yamamoto, K., Miki, Y., Sato, M., Taketomi, Y., Gelb, M.H., Lambeau, G. and Murakami, M.
  • Organizer: 5th International Conference on Phospholipase A_2 Mediates Signaling in Translational Medicine
  • Place of Presentation: New Orleans(米国)
  • Year and Date: 20130520-21
• [Presentation] 皮膚病態生理機能におけるIIE型分泌性ホスホリパーゼA_2の役割 (2012)
  • Author(s): 山本圭、佐藤弘泰、佐藤真利子、三木寿美、武富芳隆、村上誠
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] Secreted phospholipase A_2s in skin homeostasis (2011)
  • Author(s): Yamamoto, K., Shimo, K., Miki, Y., Sato, M., Taketomi, Y., Ikeda, K., Nakanishi, H., Taguchi, R., Gelb, M.H., Lambeau, G., and Murakami, M.
  • Organizer: New Aspect of Phospholipid Biology and Medicine 2011
  • Place of Presentation: 福岡
  • Year and Date: 2011-11-15
• [Presentation] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin (2011)
  • Author(s): Yamamoto, K., Taketomi, Y., Miki, Y., Sato, H., Ikeda, K., Nakanishi, H., Taguchi, R., and Murakami, M.
  • Organizer: The 8^<th> GERLI Lipidomics meeting
  • Place of Presentation: Lyon, France
  • Year and Date: 2011-10-27
• [Presentation] Group IIF phospholipase A_2 maintains epidermal homeostasis (2011)
  • Author(s): Yamamoto, K., Shimo, K., Miki, Y., Taketomi, Y., Ikeda, K., Nakanishi, H., Taguchi, R., Gelb, M.H., Lambeau, G., and Murakami, M.
  • Organizer: The 12^<th> International Conference on Bioactive Lipids in Inflammation, Cancer and Related Diseases
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-09-19
• [Remarks]
  • URL: http://www.igakuken.or.jp/lipid
• [Patent(Industrial Property Rights)] PLA2G2Fを指標とした表皮角化細胞の過増殖性疾患に対する薬剤スクリーニング方法 (2013)
  • Inventor(s): 村上誠、山本圭
  • Industrial Property Rights Holder: 公益財団法人東京都医学総合研究所
  • Industrial Property Number: 特願2013-240871
  • Filing Date: 2013-11-21
  • Overseas
• [Patent(Industrial Property Rights)] PLA2G2Fを指標とした抗皮膚癌薬のスクリーニング方法 (2012)
  • Inventor(s): 村上誠、山本圭
  • Industrial Property Rights Holder: 公益財団法人東京都医学総合研究所
  • Industrial Property Number: 特願2012-255316
  • Filing Date: 2012-11-21
  • Overseas