Anti-inflammatory effect of methyl dehydrojasmonate (J2) is mediated by the NF-κB pathway

Abstract

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.

Methyl 5-Chloro-4,5-didehydrojasmonate (J7) Inhibits Macrophage-Derived Chemokine Production <i>via</i> Down-Regulation of the Signal Transducers and Activators of Transcription 1 Pathway in HaCaT Human Keratinocytes

“…Furthermore, we have been reported that J2 inhibits the inflammatory mediators by LPS via the inhibition of NF-κB signal. 5) However, as shown in Fig. 3, J2 showed no effect on MDC production by IFN-γ and TNF-α.…”

“…Furthermore, a new synthetic methyl dehydrojasmonate compound, methyl 5-chloro-4,5-didehydrojasmonate (J7), also showed inhibitory activity against LPS-induced inflammatory mediators in murine macrophages. [4][5][6] However, the ability of jasmonic acid, methyl jasmonate, J2, and J7 to regulate the expression of mediators associated with inflammatory skin conditions has not yet been assessed in keratinocytes.…”

Cyclooxygenase-2 and MicroRNA-155 Expression Are Elevated in Asthmatic Airway Smooth Muscle Cells

“…Although several microRNAs can theoretically bind the 39 untranslated region and regulate the stability of COX-2 transcripts, we focused on miR-155 because it has been associated with proinflammatory effects that promote cytokine-responsive gene expression in several lung cell types (18,29). MiR-155 abundance was assayed after cytokine or cytomix stimulation, and levels were compared between nonasthmatic and asthmatic hASMCs.…”

“…Recent studies in fibroblasts, chondrocytes, and cancer cells clearly show miRNA-mediated regulation of COX-2 transcript stability (17,19,40). We then investigated a role for miR-155 in regulating COX-2 protein abundance because miR-155 promotes cytokine responsive gene expression in other cell types, including enhancement of COX-2 expression in RAW264.7 cells (18,30,41). Furthermore, studies in miR-155 knockout mice have demonstrated that the miRNA promotes allergic airway inflammation and mucus hypersecretion in asthma (42).…”

“…Other studies show an up-regulation of COX-2 and its reaction products in asthma (14,15). Epigenetic regulation of COX-2 expression is an emerging area of interest, and controller mechanisms include microRNAs (e.g., microRNA [miR]-155) and histone posttranslation modifications (e.g., acetylation) (16)(17)(18)(19). Indeed, reduced histone acetylation and miR-146a expression have been linked to alterations in COX-2 expression in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, respectively (17,20).…”