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IL-4 and IL-13 inhibit IL-1β and TNF-α induced kinin B 1 and B2 receptors through a STAT6-dependent mechanism
  • Umeå University
  • Universidade Estadual Paulista (UNESP)
  • Universidade de São Paulo (USP)
  • University of Gothenburg
  • 0007-1188
  • 1476-5381
Background and Purpose Bone resorption induced by interleukin-1β (IL-1β) and tumour necrosis factor (TNF-α) 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-1β or TNF-α 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-1β was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1β 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. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
Issue Date: 
British Journal of Pharmacology, v. 169, n. 2, p. 400-412, 2013.
Time Duration: 
  • interleukin-1β
  • interleukin-13
  • interleukin-4
  • kinin receptors
  • STAT6
  • tumour necrosis factor-α
  • arginine
  • bradykinin B1 receptor
  • bradykinin B2 receptor
  • bradykinin B2 receptor agonist
  • bradykinin derivative
  • calcium
  • interleukin 13
  • interleukin 1beta
  • interleukin 4
  • lysine
  • messenger RNA
  • small interfering RNA
  • STAT6 protein
  • tumor necrosis factor alpha
  • animal cell
  • animal experiment
  • animal model
  • calcium cell level
  • calvaria
  • cell strain
  • cell strain mg 63
  • controlled study
  • fibroblast
  • gene expression
  • gingiva
  • human
  • human cell
  • ligand binding
  • mouse
  • nonhuman
  • osteoblast
  • priority journal
  • protein expression
  • protein function
  • protein protein interaction
  • receptor binding
  • RNA interference
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Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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