| Autor: |
Zarpelon, Ac, Cunha, Tm, Alves-Filho, Jc, Pinto, Lg, Ferreira, Sh, McInnes, Ib, Xu, D, Liew, Fy, Cunha, Fq, Verri Jr, Wa, Zarpelon, A C, Cunha, T M, Alves-Filho, J C, Pinto, L G, Ferreira, S H, McInnes, I B, Liew, F Y, Cunha, F Q, Verri, W A Jr |
| Zdroj: |
British Journal of Pharmacology; May2013, Vol. 169 Issue 1, p90-101, 12p |
| Abstrakt: |
Background and Purpose: IL-33 signals through ST2 receptors and induces adaptive and innate inflammation. IL-33/ST2 is involved in adaptive inflammation-induced pain. Here, we have investigated the contribution of IL-33/ST2-triggered mechanisms to carrageenin-induced innate inflammation.Experimental Approach: Carrageenin- and IL-33-induced inflammatory responses were assessed in BALB/c- (WT) and ST2-deficient ((-/-) ) mice as follows: oedema (plethysmometer), myeloperoxidase activity (colorimetric assay), mechanical hyperalgesia (electronic version of von Frey filaments), cytokine levels (ELISA), PGE2 (RIA), mRNA expression (quantitative PCR), drug treatments targeting leukocyte recruitment (fucoidin), TNF-α (infliximab), CXCL1 (antibody to CXCL1), IL-1 (IL-1ra), endothelin ETA (clazosentan) and ETB (BQ788) receptors and COX (indomethacin).Key Results: Carrageenin injection increased ST2 and IL-33 mRNA expression and IL-33 production in paw skin samples. Carrageenin-induced paw oedema, hyperalgesia and myeloperoxidase activity were reduced in ST2(-/-) compared with WT mice, effects mimicked by IL-33 injection in the paw. Furthermore, IL-33-induced hyperalgesia was reduced by fucoidin suggesting a role for recruited leukocytes in its hyperalgesic effect. IL-33-induced hyperalgesia in naïve mice was reduced by treatments targeting TNF, CXCL1, IL-1, endothelin receptors and COX while carrageenin-induced ST2-dependent TNF-α, CXCL1, IL-1β, IL-10 and PGE2 production and preproET-1 mRNA expression. Combining IL-33 and carrageenin at doses that were ineffective as single treatment induced significant hyperalgesia, oedema, myeloperoxidase activity and cytokine production in a ST2-dependent manner.Conclusions and Implications: IL-33/ST2 signalling triggers the production of inflammatory mediators contributing to carrageenin-induced inflammation. These data reinforces the importance of IL-33/ST2 signalling as a target in innate inflammation and inflammatory pain. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text