IL-4 and IL-13 inhibit IL-1 beta and TNF-alpha induced kinin B-1 and B-2 receptors through a STAT6-dependent mechanism

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dc.contributor.authorSouza, P. P. C.
dc.contributor.authorBrechter, A. B.
dc.contributor.authorReis, R. I. [UNIFESP]
dc.contributor.authorCosta, C. A. S.
dc.contributor.authorLundberg, P.
dc.contributor.authorLerner, U. H.
dc.contributor.institutionUmea Univ
dc.contributor.institutionUniv Estadual Paulista
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Gothenburg
dc.date.accessioned2016-01-24T14:31:37Z
dc.date.available2016-01-24T14:31:37Z
dc.date.issued2013-05-01
dc.description.abstractBackground and Purpose Bone resorption induced by interleukin-1 (IL-1) and tumour necrosis factor (TNF-) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation-induced bone resorption can be impaired by IL-4 and IL-13. the aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL-4 and IL-13. Experimental Approach We examined effects in a human osteoblastic cell line (MG-63), primary human gingival fibroblasts and mouse bones by IL-4 and IL-13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6-/- mice. Key Results IL-4 and IL-13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL-1 or TNF- in MG-63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. the burst of intracellular calcium induced by either bradykinin (B2 agonist) or des-Arg10-Lys-bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL-1 was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1 was decreased by IL-4. in calvarial bones from Stat6-deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL-4 was decreased. Conclusions and Implications These data show, for the first time, that IL-4 and IL-13 decrease kinin receptors in a STAT6-dependent mechanism, which can be one important mechanism by which these cytokines exert their anti-inflammatory effects and impair bone resorption.en
dc.description.affiliationUmea Univ, Dept Mol Periodontol, SE-90187 Umea, Sweden
dc.description.affiliationUniv Estadual Paulista, Dept Physiol & Pathol, Araraquara Sch Dent, Araraquara, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Nephrol Div, São Paulo, Brazil
dc.description.affiliationUniv Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Nephrol Div, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSwedish Research Council for Medicine
dc.description.sponsorshipSwedish Rheumatism Association
dc.description.sponsorshipCounty Council of Vasterbotten
dc.description.sponsorshipSwedish Dental Society, Combine, Salus Ansvar
dc.description.sponsorshipLundberg Foundation
dc.description.sponsorshipALF/LUA grant from the Sahlgrenska University Hospital,
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDALF/LUA grant from the Sahlgrenska University Hospital,: 2008/58958-7
dc.description.sponsorshipIDALF/LUA grant from the Sahlgrenska University Hospital,: 2008/07221-4
dc.description.sponsorshipIDFAPESP: 2008/58958-7
dc.description.sponsorshipIDFAPESP: 2008/07221-4
dc.description.sponsorshipIDCNPq: 301291/2010 PQ
dc.format.extent400-412
dc.identifierhttp://dx.doi.org/10.1111/bph.12116
dc.identifier.citationBritish Journal of Pharmacology. Hoboken: Wiley-Blackwell, v. 169, n. 2, p. 400-412, 2013.
dc.identifier.doi10.1111/bph.12116
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36240
dc.identifier.wosWOS:000318234600013
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsAcesso aberto
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectinterleukin-4en
dc.subjectinterleukin-13en
dc.subjectinterleukin-1en
dc.subjecttumour necrosis factor-en
dc.subjectkinin receptorsen
dc.subjectSTAT6en
dc.titleIL-4 and IL-13 inhibit IL-1 beta and TNF-alpha induced kinin B-1 and B-2 receptors through a STAT6-dependent mechanismen
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