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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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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Autor(es):
Souza, P. P. C. [1, 2] ; Brechter, A. B. [1] ; Reis, R. I. [3] ; Costa, C. A. S. [2] ; Lundberg, P. [1] ; Lerner, U. H. [1, 4]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Umea Univ, Dept Mol Periodontol, SE-90187 Umea - Sweden
[2] Univ Estadual Paulista, Dept Physiol & Pathol, Araraquara Sch Dent, Araraquara - Brazil
[3] Univ Fed Sao Paulo, Dept Med, Nephrol Div, Sao Paulo - Brazil
[4] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg - Sweden
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: British Journal of Pharmacology; v. 169, n. 2, p. 400-412, MAY 2013.
Citações Web of Science: 15
Resumo

Background 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. (AU)

Processo FAPESP: 08/58958-7 - Cininas e prostaglandinas na reabsorcao ossea inflamatoria.
Beneficiário:Carlos Alberto de Souza Costa
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/07221-4 - Cininas e prostaglandinas na reabsorção óssea inflamatória
Beneficiário:Pedro Paulo Chaves de Souza
Linha de fomento: Bolsas no Brasil - Pós-Doutorado