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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain

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Autor(es):
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Zarpelon, Ana C. [1] ; Rodrigues, Francielle C. [1] ; Lopes, Alexandre H. [2] ; Souza, Guilherme R. [2] ; Carvalho, Thacyana T. [1] ; Pinto, Larissa G. [2] ; Xu, Damo [3] ; Ferreira, Sergio H. [2] ; Alves-Filho, Jose C. [2] ; McInnes, Iain B. [3] ; Ryffel, Bernhard [4, 5] ; Quesniaux, Valerie F. J. [4, 5] ; Reverchon, Flora [4, 5] ; Mortaud, Stephane [4, 5] ; Menuet, Arnaud [4, 5] ; Liew, Foo Y. [3, 6] ; Cunha, Fernando Q. [2] ; Cunha, Thiago M. [2] ; Verri, Jr., Waldiceu A. [1]
Número total de Autores: 19
Afiliação do(s) autor(es):
[1] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Ciencias Patol, BR-86057970 Londrina, Parana - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil
[3] Univ Glasgow, Glasgow Biomed Res Ctr, Div Immunol Infect & Inflammat, Glasgow, Lanark - Scotland
[4] Ctr Natl Rech Sci Expt & Mol Immunol & Neurogenet, Unites Mixtes Rech 7355, Orleans - France
[5] Univ Orleans, Immunol & Neurogenet Expt & Mol, Orleans - France
[6] Soochow Univ, Sch Biol & Basic Med Sci, Suzhou - Peoples R China
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: FASEB JOURNAL; v. 30, n. 1, p. 54-65, JAN 2016.
Citações Web of Science: 51
Resumo

Neuropathic pain from injury to the peripheral and CNS represents a major health care issue. We have investigated the role of IL-33/IL-33 receptor (ST2) signaling in experimental models of neuropathic pain in mice. Chronic constriction injury (CCI) of the sciatic nerve induced IL-33 production in the spinal cord. IL-33/citrine reporter mice revealed that oligodendrocytes are the main cells expressing IL-33 within the spinal cord together with a minor expression by neurons, microglia. and astrocytes. CCI-induced mechanical hyperalgesia was reduced in IL-33R (ST2) (-/-) mice compared with wild-type (WT) mice. Intrathecal treatment of WT mice with soluble IL-33 receptor (IL-33 decoy receptor) markedly reduced CCI-induced hyperalgesia. Consistent with these observations, intrathecal injection of IL-33 enhanced CCI hyperalgesia and induced hyperalgesia in naive mice. IL-33-mediated hyperalgesia during CCI was dependent on a reciprocal relationship with TNF-alpha and IL-1 beta. IL-33-induced hyperalgesia was markedly attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK, and JNK), NF-kappa B, and also by the inhibitors of glial cells (microglia and astrocytes). Furthermore, targeting these signaling pathways and cells inhibited IL-33-induced TNF-alpha a and IL-1 beta production in the spinal cord. Our study, therefore, reveals an important role of oligodendrocyte-derived IL-33 in neuropathic pain.-Zarpelon, A. C., Rodrigues, F. C., Lopes, A. H., Souza, G. R., Carvalho, T. T., Pinto, L. G., Xu, D., Ferreira, S. H., Alves-Filho, J. C., McInnes, I. B., Ryffel, B., Quesniaux, V. F. J., Reverchon, F., Mortaud, S., Menuet, A., Liew, F. Y., Cunha, F. Q., Cunha, T. M., Verri, Jr., W. A. Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain. FASEB J. 30, 54-65 (2016). www.fasebj.org (AU)

Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Temático