IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: role of cytokines, endothelin-1 and prostaglandin E2

Zarpelon, A.C., Cunha, T.M., Alves-Filho, J.C., Pinto, L.G., Ferreira, S.H., McInnes, I.B. , Xu, D., Liew, F.Y., Cunha, F.Q. and Verri, W.A. (2013) IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: role of cytokines, endothelin-1 and prostaglandin E2. British Journal of Pharmacology, 169(1), pp. 90-101. (doi:10.1111/bph.12110) (PMID:23347081) (PMCID:PMC3632241)

Full text not currently available from Enlighten.

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo
Authors: Zarpelon, A.C., Cunha, T.M., Alves-Filho, J.C., Pinto, L.G., Ferreira, S.H., McInnes, I.B., Xu, D., Liew, F.Y., Cunha, F.Q., and Verri, W.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:British Journal of Pharmacology
Publisher:John Wiley & Sons, Inc.
ISSN:0007-1188
ISSN (Online):1476-5381

University Staff: Request a correction | Enlighten Editors: Update this record