title: Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway.
abstract: The inhibitory effect of four structurally related flavonoids, apigenin, baicalein, luteolin and quercetin on the matrix metalloproteinase (MMP)-9 and -13 expressions in osteoblasts was investigated. Treatment with IL-1β induced both MMP-9 and -13 mRNA expressions as measured by quantitative real-time PCR. Luteolin and apigenin decreased IL-1β-induced MMP-9 and -13 mRNA expressions, whereas baicalein and quercetin showed little effects. Related to signalling, treatment with IL-1β induced ERK phosphorylation as measured by Western blotting. Further studies showed that transfection with a constitutively active form of the Ras protein (Ras(V12)) induced stronger ERK phosphorylation and upregulated MMP-9 and -13 mRNA expressions. However, transfection with a dominant-negative form of the Ras protein (Ras(N17)) inhibited the ERK activation and MMP-9 and -13 mRNA expressions induced by IL-1β, which supported the involvement of ERK signalling in IL-1β-induced MMP-9 and -13 expressions. Treatment with luteolin effectively inhibited the IL-1β-induced ERK activation in dose-dependent manner. Taken together, luteolin might inhibit IL-1β-induced MMP-9 and -13 expressions, in part, via inhibition of ERK signalling.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, Korea.
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ahn
authors.forename: Seon Beom
authors.initials: SB
authors.lastname: Kim
authors.forename: Young Choong
authors.initials: YC
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation; D053583:Interleukin-1beta / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9; D047311:Luteolin