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Title: 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
Authors: Souza, P. P. C.
Brechter, A. B.
Reis, R. I. [UNIFESP]
Costa, C. A. S.
Lundberg, P.
Lerner, U. H.
Umea Univ
Univ Estadual Paulista
Universidade Federal de São Paulo (UNIFESP)
Univ Gothenburg
Keywords: interleukin-4
tumour necrosis factor-
kinin receptors
Issue Date: 1-May-2013
Publisher: Wiley-Blackwell
Citation: British Journal of Pharmacology. Hoboken: Wiley-Blackwell, v. 169, n. 2, p. 400-412, 2013.
Abstract: 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.
ISSN: 0007-1188
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