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- Title
6,7-DIMETHOXY-4-METHYLCOUMARIN SUPPRESSES PRO-INFLAMMATORY MEDIATOR EXPRESSION THROUGH INACTIVATION OF THE NF-κB AND MAPK PATHWAYS IN LPS-INDUCED RAW 264.7 CELLS.
- Authors
Kil-Nam Kim; Hye-Won Yang; Seok-Chun Ko; Yeong-Jong Ko; Eun-A Kim; Seong Woon Roh; Eun-Yi Ko; Ginnae Ahn; Soo-Jin Heo; You-Jin Jeon; Weon-Jong Yoon; Chang-Gu Hyun; Daekyung Kim
- 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 downregulated 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 antiinflammatory 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 I?B-a 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.
- Subjects
LIPOPOLYSACCHARIDES; INFLAMMATORY mediators; LABORATORY mice; NITRIC oxide; CYCLOOXYGENASE 2
- Publication
EXCLI Journal, 2014, Vol 13, p792
- ISSN
1611-2156
- Publication type
Article