title: 12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia.
abstract: Jasmonates are plant lipid-derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)-induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan; Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Taki-Nakano
authors.affiliation: Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kotera
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan; School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. Electronic address: ohta.h.ab@m.titech.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohta
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology*; D054883:Oxylipins / Q000008:administration & dosage*; D010936:Plant Extracts / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D054883:Oxylipins; D010936:Plant Extracts; C025999:12-oxophytodienoic acid
keywords: Anti-inflammatory activity; Jasmonates; Microglia; OPDA; Plant oxylipins