Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation.
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| Abstract |
Lipid mediators are known to play crucial roles not only in the onset of the inflammatory response but also in the induction of resolution of inflammation. Here, we report that palmitoylethanolamide (PEA), an endogenous N-acylethanolamine, can suppress the inflammation induced by Toll-like receptor (TLR) signaling both in vitro and in vivo. PEA was found to be significantly reduced in the serum and spleen of lupus-prone MRL/lpr mice analyzed by lipidomics. PEA suppressed pro-inflammatory cytokine production in a mouse macrophage cell line stimulated with TLR ligands such as lipopolysaccharide, peptidoglycan, poly (I:C), imiquimod, and CpG-ODN. PEA also inhibited both mRNA and protein levels of IL-6 in bone marrow-derived dendritic cells (BMDCs) and B cells stimulated with CpG-ODN. Augmentation of cell surface CD86 and CD40 on BMDCs and B cells, IgM production, and cell proliferation of B cells in response to CpG-ODN were attenuated by PEA. Moreover, PEA treatment significantly reduced mortality and serum IL-6 levels in mice injected with CpG-ODN plus D-galactosamine. Taken together, PEA ameliorates inflammation induced by TLR signaling, which could be a novel therapeutic target for inflammatory disorders.
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| Authors | Takashi Ozaki, Naganori Kamiyama, Benjawan Saechue, Yasuhiro Soga, Ryo Gotoh, Tatsuya Nakayama, Chiaki Fukuda, Astri Dewayani, Thanyakorn Chalalai, Shimpei Ariki, Sotaro Ozaka, Akira Sonoda, Haruna Hirose, Yoshiko Gendo, Kaori Noguchi, Nozomi Sachi, Shinya Hidano, Keisuke Maeshima, Koro Gotoh, Takayuki Masaki, Koji Ishii, Yoshio Osada, Hirotaka Shibata, Takashi Kobayashi |
| Journal | Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 27 Issue 7 Pg. 493-504 (Jul 2022) ISSN: 1365-2443 [Electronic] England |
| PMID | 35485445 (Publication Type: Journal Article) |
| Copyright | © 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd. |
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