Anti-inflammatory effect of methyl dehydrojasmonate (J2) is mediated by the NF-κB pathway.
Inflammation as a major defense mechanism against pathogens is modulated by diverse microbial products. A variety of plant and microbial products interacting with Toll-like receptors initiate a wide spectrum of responses from phagocytosis to cytokine production, which modulates inflammation. Jasmonates are fatty acid-derived cyclopentanones produced by plants and lower eukaryotes that play an important role in the defense against insects. In this study, we are set up to define the molecular targets of J2 action. While the lipopolysaccharide (LPS) stimulation of macrophage cell line RAW264.7 induced TNF-α, IL-6, iNOS, and COX-2 that were associated with an increase in miR-155 and miR-146a, the J2 suppressed the induction of these inflammatory cytokines and enzymes as well as miR-155 in a dose-dependent manner. To assess the associations of miR-155 with inflammatory markers, we overexpressed miR-155 and found attenuation of COX-2 suppression with J2 treatment. Furthermore, J2 inhibited NF-κB, p65, and IκB but had no or only minimal effects on the mitogen-activated protein kinase pathway. In conclusion, the present study demonstrates that J2 suppresses LPS stimulation of RAW264.7 cells by targeting NF-κB pathways.
Lee
Hye-Ja
HJ
Department of Pharmacology, College of Medicine, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea.
Maeng
Kyungah
K
Dang
Hung-The
HT
Kang
Gyeoung-Jin
GJ
Ryou
Chongsuk
C
Jung
Jee H
JH
Kang
Hee-Kyoung
HK
Prchal
Josef T
JT
Yoo
Eun-Sook
ES
Yoon
Donghoon
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology* / Q000633:toxicity; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D054883:Oxylipins / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D003517:Cyclopentanes; D016207:Cytokines; D008070:Lipopolysaccharides; D035683:MicroRNAs; D016328:NF-kappa B; D054883:Oxylipins; C519297:methyl 4,5-didehydrojasmonate; D048051:p38 Mitogen-Activated Protein Kinases