Authors: Kim, Kil-Nam
Yang, Hye-Won
Ko, Seok-Chun
Ko, Yeong-Jong
Kim, Eun-A
Roh, Seong Woon
Ko, Eun-Yi
Ahn, Ginnae
Heo, Soo-Jin
Jeon, You-Jin
Yoon, Weon-Jong
Hyun, Chang-Gu
Kim, Daekyung
Title: 6,7-Dimethoxy-4-methylcoumarin suppresses pro-inflammatory mediator expression through inactivation of the NF-kappaB and MAPK pathways in LPS-induced RAW 264.7 cells
Language (ISO): en
Abstract: In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin (DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism through which this inhibition occurred. Our results indicated that DMC down regulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, thereby reducing the production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. To elucidate the mechanism underlying the anti- inflammatory activity of DMC, we assessed its effects on the mitogen-activated protein kinase (MAPK) pathway and the activity and expression of nuclear transcription factor kappa-B (NF-κB). The experiments demonstrated that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it attenuated LPS-induced NF-κB activation via the inhibition of IκB-α phosphorylation. Taken together, these data suggest that DMC exerts its anti-inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated NF-κB and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.
Subject Headings: 6,7-Dimethoxy-4-methylcoumarin (DMC)
anti-inflammatory
RAW 264.7 cells
NF-κB
MAPKs
URI: http://hdl.handle.net/2003/33712
http://dx.doi.org/10.17877/DE290R-6945
Issue Date: 2014-07-21
Appears in Collections:Original Articles

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