p38 MAPK regulates IL-1β induced IL-6 expression through mRNA stability in osteoblasts

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dc.contributor.authorPatil, Chetan
dc.contributor.authorZhu, Xinsheng
dc.contributor.authorRossa Júnior, Carlos [UNESP]
dc.contributor.authorKim, Young Joon
dc.contributor.authorKirkwood, Keith L.
dc.contributor.institutionState Univ. of New York at Buffalo
dc.contributor.institutionChonnam National University
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Michigan
dc.date.accessioned2014-05-27T11:21:05Z
dc.date.available2014-05-27T11:21:05Z
dc.date.issued2004-06-08
dc.description.abstractOsteoblast-derived IL-6 functions in coupled bone turnover by supporting osteoclastogenesis favoring bone resorption instead of bone deposition. Gene regulation of IL-6 is complex occurring both at transcription and post-transcription levels. The focus of this paper is at the level of mRNA stability, which is important in IL-6 gene regulation. Using the MC3T3-E1 as an osteoblastic model, IL-6 secretion was dose dependently decreased by SB203580, a p38 MAPK inhibitor. Steady state IL-6 mRNA was decreased with SB203580 (2 μM) ca. 85% when stimulated by IL-1β (1-5 ng/ ml). These effects require de novo protein synthesis as they were inhibited by cycloheximide. p38 MAPK had minor effects on proximal IL-6 promoter activity in reporter gene assays. A more significant effect on IL-6 mRNA stability was observed in the presence of SB203580. Western blot analysis confirmed that SB203580 inhibited p38 MAP kinase, in response to IL-1β in a dose dependent manner in MC3T3-E1 cells. Stably transfected MC3T3-E1 reporter cell lines (MC6) containing green fluorescent protein (GFP) with the 3′untranslated region of IL-6 were constructed. Results indicated that IL-1β, TNFα, LPS but not parathyroid hormone (PTH) could increase GFP expression of these reporter cell lines. Endogenous IL-6 and reporter gene eGFP-IL-6 3′UTR mRNA was regulated by p38 in MC6 cells. In addition, transient transfection of IL-6 3′UTR reporter cells with immediate upstream MAP kinase kinase-3 and -6 increased GFP expression compared to mock transfected controls. These results indicate that p38 MAPK regulates IL-1β-stimulated IL-6 at a post transcriptional mechanism and one of the primary targets of IL-6 gene regulation is the 3′UTR of IL-6.en
dc.description.affiliationDepartment of Oral Biology State Univ. of New York at Buffalo, Buffalo, NY
dc.description.affiliationDept. of Periodont. and Endodontics State Univ. of New York at Buffalo, Buffalo, NY
dc.description.affiliationDept. of Pharmacology and Toxicology State Univ. of New York at Buffalo, Buffalo, NY
dc.description.affiliationDepartment of Periodontics Chonnam National University, Kwang-Ju
dc.description.affiliationDepartment of Surgery and Diagnosis School of Dentistry at Araraquara UNESP
dc.description.affiliationDept. of Periodont./Prev./Geriatrics School of Dentistry University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109
dc.description.affiliationUnespDepartment of Surgery and Diagnosis School of Dentistry at Araraquara UNESP
dc.format.extent213-233
dc.identifierhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1201547/
dc.identifier.citationImmunological Investigations, v. 33, n. 2, p. 213-233, 2004.
dc.identifier.file2-s2.0-2542469918.pdf
dc.identifier.issn0882-0139
dc.identifier.scopus2-s2.0-2542469918
dc.identifier.urihttp://hdl.handle.net/11449/67765
dc.language.isoeng
dc.relation.ispartofImmunological Investigations
dc.relation.ispartofjcr2.588
dc.relation.ispartofsjr0,740
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectARE
dc.subjectGene expression
dc.subjectGFP
dc.subjectIL-1β
dc.subjectIL-6
dc.subjectMRNA Stability
dc.subjectOsteoblasts
dc.subjectp38 MAPK
dc.subject4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole
dc.subjectcycloheximide
dc.subjectgreen fluorescent protein
dc.subjectinterleukin 1beta
dc.subjectinterleukin 6
dc.subjectlipopolysaccharide
dc.subjectmessenger RNA
dc.subjectmitogen activated protein kinase p38
dc.subjectsynaptophysin
dc.subjecttumor necrosis factor alpha
dc.subjectanimal cell
dc.subjectbone turnover
dc.subjectcell strain
dc.subjectcell strain MC 3T3 E1
dc.subjectcell strain MC6
dc.subjectcontrolled study
dc.subjectcytokine release
dc.subjectdose response
dc.subjectgene control
dc.subjectgenetic analysis
dc.subjectgenetic transfection
dc.subjectmouse
dc.subjectnonhuman
dc.subjectosteoblast
dc.subjectosteoclast
dc.subjectosteolysis
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein processing
dc.subjectprotein synthesis
dc.subjectpublication
dc.subjectregulatory mechanism
dc.subjectreporter gene
dc.subjectRNA stability
dc.subjectsteady state
dc.subjectWestern blotting
dc.subject3' Untranslated Regions
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectCell Line
dc.subjectEnzyme Inhibitors
dc.subjectGene Expression Regulation
dc.subjectGenetic Vectors
dc.subjectInterleukin-1
dc.subjectInterleukin-6
dc.subjectMice
dc.subjectMolecular Sequence Data
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectPromoter Regions (Genetics)
dc.subjectRecombinant Proteins
dc.subjectRNA Stability
dc.subjectRNA, Messenger
dc.subjectSignal Transduction
dc.titlep38 MAPK regulates IL-1β induced IL-6 expression through mRNA stability in osteoblastsen
dc.typeArtigo
unesp.author.lattes7634063102292261[3]
unesp.author.orcid0000-0003-1705-5481[3]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araraquarapt

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