Identification of palmitoylethanolamide and oleoylethanolamide with inhibitory effect on SLE-related inflammation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16155
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Oita University
• Principal Investigator: Ozaki Takashi 大分大学, 医学部, 助教 (70749374)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: パルミトイルエタノールアミド / Toll様受容体 / 脂質メディエーター / オレオイルエタノールアミド

Outline of Final Research Achievements

Palmitoylethanolamide (PEA), an endogenous N-acylethanolamide, can suppress inflammation induced by Toll-like receptor (TLR) signaling both in vitro and in vivo. PEA suppressed pro-inflammatory cytokine production in a mouse macrophage cell line (RAW 264.7) in response to TLR ligands such as lipopolysaccharide, peptidoglycan, poly (I:C), imiquimod and CpG-ODN. PEA inhibited both mRNA and protein levels of IL-6 in bone marrow derived dendritic cells (BMDCs) and B cells stimulated with CpG-ODN. In addition, co-stimulatory molecules such as CD80 and CD40 on BMDCs and B cells, together with IgM production and cell proliferation of B cells, were attenuated by PEA. Moreover, PEA significantly reduced mortality and serum IL-6 levels in mice injected with CpG-ODN plus D-galactosamine. Taken together, these results suggest that PEA ameliorates inflammation by inhibiting TLR signaling, which could be a novel therapeutic target for inflammatory disorders.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

近年、抗炎症性の脂質メディエーターが注目される中において、本研究を通じてパルミトイルエタノールアミド(PEA)が各種免疫担当細胞におけるTLR9刺激を介した炎症性サイトカイン産生や細胞表面マーカー発現、細胞増殖や抗体産生に対していずれも抑制的に作用することが明らかとなった。また、PEAの抗炎症作用はSeptic shockモデルマウスの生体内においても発揮されることも見出した。将来的にSLEをはじめとするTLRが関連した炎症性疾患の治療薬として、PEAが創薬のターゲットとなり得る可能性が示唆される。