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Il-4 and Il-13 Inhibit Il-1β and Tnf-α Induced Kinin B(1) and B(2) Receptors Through a Stat6 Dependent Mechanism.
MedLine Citation:
PMID:  23351078     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Bone resorption induced by interleukin-1β (IL-1 β) 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 B(1) and B(2) 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 B(1) and B(2) 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 B(1) and B(2) 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 (B(2) agonist) or des-Arg(10) -Lys-bradykinin (B(1) agonist) in gingival fibroblasts pretreated with IL-1β was impaired by IL-4. Similarly, the increased binding of B(1) and B(2) 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.
Authors:
P P C Souza; A B Brechter; R I Reis; C A S Costa; P Lundberg; U H Lerner
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-28
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
Affiliation:
Department of Molecular Periodontology, Umeå University, Umeå, Sweden; Department of Physiology and Pathology, Araraquara School of Dentistry,University Estadual Paulista, Araraquara, Brazil.
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