Effects of a tetramethoxyhydroxyflavone p7f on the expression of inflammatory mediators in LPS-treated human synovial fibroblast and macrophage cells.
The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1beta or TNF-alpha induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin E2 in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1beta and thus proliferates), revealing that p7F inhibited IL-1beta-induced proliferation of D10S Th2 cells in a doseresponse manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkappaB degradation and NF-kappaB activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an antiinflammatory agent for inhibiting inflammatory responses.
Yoon
Do-Young
DY
Division of Bioscience and Biotechnology, Konkuk University, Hwayang dong 1, Kwangjin gu, Seoul 143-701, Korea.
Cho
Min-Chul
MC
Kim
Jung-Hee
JH
Kim
Eun-Jin
EJ
Kang
Jeong-Woo
JW
Seo
Eun-Hee
EH
Shim
Jung-Hyun
JH
Kim
Soo-Hyun
SH
Lee
Hee-Gu
HG
Oh
Goo-Taeg
GT
Hong
Jin-Tae
JT
Park
Joo-Won
JW
Kim
Jong-Wan
JW
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002061:Bursa, Synovial / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
C501197:5,6,3',5'-tetramethoxy-7,4'-hydroxyflavone; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D017382:Reactive Oxygen Species