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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: British Journal of Pharmacology; v. 169, n. 2, p. 400-412, MAY 2013.
• Web of Science Citations: 15

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. (AU)

• FAPESP's process: 08/07221-4 - Kinins and prostaglandins in inflammatory bone resorption
• Grantee: Pedro Paulo Chaves de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral