Abstract
Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1β and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1β and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers.
Highlights
Inflammation, the immediate response of the body to a damage, is triggered by noxious stimuli and conditions, such as infection and tissue injury [1]
Macrophages produce many pro-inflammatory cytokines; among those produced by M1 macrophages are IL-1, IL-4, IL-6, IL-12, and TNFα, while those produced by M2 macrophages include
To evaluate the effects of Decursinol angelate (DA) treatment on cytokine production in phorbol 12-myristate 13-acetate (PMA)-stimulated macrophages, we analyzed the mRNA levels of IL-1β, IL-4, IL-6, and IL-10 through Reverse-Transcription Polymerase Chain Reaction (RT-PCR) using
Summary
Inflammation, the immediate response of the body to a damage, is triggered by noxious stimuli and conditions, such as infection and tissue injury [1]. TAM activation or macrophage polarization by inflammatory cytokines (IFN-γ, TNF, and IL-12), anti-inflammatory cytokines (IL-4 and IL-10), or bacterial lipopolysaccharide (LPS) is the primary process involved in inflammation-associated cancers. This process results in the loss of homeostatic tissue architecture followed by immune suppression [9,10]. Studies have reported that decursin inhibits matrix metallopeptidase 9 (MMP-9)-induced cytoskeletal rearrangement by suppressing phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and NFκB activation in fibrosarcoma and breast cancer cell lines [26]. DA inhibited the differentiation and polarization of macrophages by suppressing the expression of inflammatory cytokines and the MAPK and NFκB pathways, as well as by reducing NADPH oxidase (NOX) and iNOS levels in LPS and TPA-induced inflammatory models
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