Verri, Jr., W. A., Guerrero, A. T. G., Fukada, S. Y., Valerio, D. A., Cunha, T. M., Xu, D., Ferreira, S. H., Liew, F. Y. and Cunha, F. Q. (2008) IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice. Proceedings of the National Academy of Sciences of the United States of America, 105(7), pp. 2723-2728. (doi: 10.1073/pnas.0712116105)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.0712116105
Abstract
IL-33, a new member of the IL-1 family, signals through its receptor ST2 and induces T helper 2 (Th2) cytokine synthesis and mediates inflammatory response. We have investigated the role of IL-33 in antigen-induced hypernociception. Recombinant IL-33 induced cutaneous and articular mechanical hypernociception in a time- and dose-dependent manner. The hypernociception was inhibited by soluble (s) ST2 (a decoy receptor of IL-33), IL-1 receptor antagonist (IL-1ra), bosentan [a dual endothelin (ET)A/ETB receptor antagonist], clazosentan (an ETA receptor antagonist), or indomethacin (a cyclooxygenase inhibitor). IL-33 induced hypernociception in IL-18−/− mice but not in TNFR1−/− or IFNγ−/− mice. The IL-33-induced hypernociception was not affected by blocking IL-15 or sympathetic amines (guanethidine). Furthermore, methylated BSA (mBSA)-induced cutaneous and articular mechanical hypernociception depended on TNFR1 and IFNγ and was blocked by sST2, IL-1ra, bosentan, clazosentan, and indomethacin. mBSA also induced significant IL-33 and ST2 mRNA expression. Importantly, we showed that mBSA induced hypernociception via the IL-33 → TNFα → IL-1β → IFNγ → ET-1 → PGE2 signaling cascade. These results therefore demonstrate that IL-33 is a key mediator of immune inflammatory hypernociception normally associated with a Th1 type of response, revealing a hitherto unrecognized function of IL-33 in a key immune pharmacological pathway that may be amenable to therapeutic intervention.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Liew, Prof Foo and Xu, Dr Damo and Fukada, Dr Sandra |
| Authors: | Verri, Jr., W. A., Guerrero, A. T. G., Fukada, S. Y., Valerio, D. A., Cunha, T. M., Xu, D., Ferreira, S. H., Liew, F. Y., and Cunha, F. Q. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Related URLs: |
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