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

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

Autor Souza, P. P. C. Google Scholar
Brechter, A. B. Google Scholar
Reis, R. I. Autor UNIFESP Google Scholar
Costa, C. A. S. Google Scholar
Lundberg, P. Google Scholar
Lerner, U. H. Google Scholar
Instituição Umea Univ
Univ Estadual Paulista
Universidade Federal de São Paulo (UNIFESP)
Univ Gothenburg
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.
Palavra-chave interleukin-4
interleukin-13
interleukin-1
tumour necrosis factor-
kinin receptors
STAT6
Idioma Inglês
Financiador Swedish Research Council for Medicine
Swedish Rheumatism Association
County Council of Vasterbotten
Swedish Dental Society, Combine, Salus Ansvar
Lundberg Foundation
ALF/LUA grant from the Sahlgrenska University Hospital,
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento ALF/LUA grant from the Sahlgrenska University Hospital,: 2008/58958-7
ALF/LUA grant from the Sahlgrenska University Hospital,: 2008/07221-4
FAPESP: 2008/58958-7
FAPESP: 2008/07221-4
CNPq: 301291/2010 PQ
Data de publicação 2013-05-01
Publicado em British Journal of Pharmacology. Hoboken: Wiley-Blackwell, v. 169, n. 2, p. 400-412, 2013.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Publicador Wiley-Blackwell
Extensão 400-412
Fonte http://dx.doi.org/10.1111/bph.12116
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000318234600013
Endereço permanente http://repositorio.unifesp.br/handle/11600/36240

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