MKK3/6-p38 MAPK negatively regulates murine MMP-13 gene expression induced by IL-1 beta and TNF-alpha in immortalized periodontal ligament fibroblasts

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dc.contributor.authorRossa, C.
dc.contributor.authorLiu, M.
dc.contributor.authorPatil, C.
dc.contributor.authorKirkwood, K. L.
dc.contributor.institutionUniversity of Michigan
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionSUNY Coll Buffalo
dc.date.accessioned2014-05-20T15:26:25Z
dc.date.available2014-05-20T15:26:25Z
dc.date.issued2005-10-01
dc.description.abstractMatrix metalloprotease-13 (MMP-13) or collagenase-3 is involved in a number of pathologic processes such as tumor metastasis and angiogenesis, osteoarthritis, rheumatoid arthritis and periodontal diseases. These conditions are associated with extensive degradation of both connective tissue and bone. This report examines gene regulation mechanisms and signal transduction pathways involved in Mmp-13 expression induced by proinflammatory cytokines in periodontal ligament (PDL) fibroblasts. Mmp-13 mRNA expression was increased 10.7 and 9.5 fold after stimulation with IL-1 beta (5 ng/mL) and TNF-alpha (10 ng/mL), respectively. However, inhibition of p38 MAPKinase with SB203580 resulted in significant (p < 0.001) induction (23.2 and 18.1 fold, respectively) of Mmp-13 mRNA as assessed by real time PCR. Negative regulation of IL-1 induced Mmp-13 expression was confirmed by inhibiting p38 MAPK gene expression with siRNA. Transient transfection of dominant negative forms of MKK3 and MKK6 also resulted in increased levels of Mmp-13 mRNA after IL-1 beta stimulation. Mmp-13 mRNA expression induced by TNF-alpha was decreased by JNK and ERK inhibition. Western blot and zymogram analysis indicated that Mmp-13 protein expression induced by the proinflammatory cytokines were also upregulated by inhibition of p38 MAPK. Reporter gene experiments using stable cell lines harboring 660-bp sequence of the murine Mmp-13 proximal promoter indicated that transcriptional mechanisms were at least partially involved in this negative regulation of Mmp-13 expression by p38 MAPK and upstream MKK3/6. These results suggest a negative transcriptional regulatory mechanism mediated by p38 MAPK and upstream MKK3/6 on Mmp-13 expression induced by proinflammatory cytokines in PDL fibroblasts. (c) 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.en
dc.description.affiliationUniv Michigan, Sch Dent, Periodont Prevent Geriat Dept, Ann Arbor, MI 48109 USA
dc.description.affiliationState Univ São Paulo, Dept Diagnost & Surg, Sch Dent Araraquara, Araraquara, SP, Brazil
dc.description.affiliationSUNY Coll Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14222 USA
dc.description.affiliationUnespState Univ São Paulo, Dept Diagnost & Surg, Sch Dent Araraquara, Araraquara, SP, Brazil
dc.format.extent478-488
dc.identifierhttp://dx.doi.org/10.1016/j.matbio.2005.06.006
dc.identifier.citationMatrix Biology. Amsterdam: Elsevier B.V., v. 24, n. 7, p. 478-488, 2005.
dc.identifier.doi10.1016/j.matbio.2005.06.006
dc.identifier.issn0945-053X
dc.identifier.urihttp://hdl.handle.net/11449/36588
dc.identifier.wosWOS:000233004500005
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofMatrix Biology
dc.relation.ispartofjcr8.136
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectMMP-13pt
dc.subjectsignal transductionpt
dc.subjectcollagenasept
dc.subjectperiodontal diseasespt
dc.subjectperiodontal ligament fibroblastspt
dc.titleMKK3/6-p38 MAPK negatively regulates murine MMP-13 gene expression induced by IL-1 beta and TNF-alpha in immortalized periodontal ligament fibroblastsen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.lattes7634063102292261[1]
unesp.author.orcid0000-0003-1705-5481[1]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araraquarapt

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