Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation

Autor(es)

Kanashiro, Alexandre ^{[1, 2]} ; Franchin, Marcelo ^[3] ; Bassi, Gabriel Shimizu ^{[4, 5]} ; Reis Santana, Denis Augusto ^[1] ; Cunha, Thiago Mattar ^[1] ; Cunha, Fernando Queiroz ^[1] ; Ulloa, Luis ^[6] ; Rodrigues, Gerson Jonathan ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Bandeirantes Ave 3900, BR-14049090 Ribeirao Preto, SP - Brazil

^[2] Fed Univ Sao Carlos UFSCAR, Dept Physiol Sci, Km 235, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Estadual Campinas, Dept Physiol Sci, Piracicaba Dent Sch, Limeira Av 901, BR-13414903 Piracicaba, SP - Brazil

^[4] Univ Sao Paulo, Dept Immunol, Ribeirao Preto Med Sch, Bandeirantes Ave 3900, BR-14049090 Ribeirao Preto, SP - Brazil

^[5] Univ Leuven, Translat Res Ctr GastroIntestinal Disorders TARGI, Intestinal Neuroimmune Interact, B-3000 Leuven - Belgium

^[6] Rutgers State Univ, Dept Surg, Ctr Immunol & Inflammat, Rutgers New Jersey Med Sch, Newark, NJ 07103 - USA

• Tipo de documento: Artigo Científico
• Fonte: FUNDAMENTAL & CLINICAL PHARMACOLOGY; v. 32, n. 2, p. 155-162, APR 2018.
• Citações Web of Science: 1

Resumo

The central nervous system controls the innate immunity by modulating efferent neuronal networks. Recently, we have reported that central brain stimulation inhibits inflammatory responses. In the present study, we investigate whether spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in experimental arthritis. Firstly, we observed that intra-articular administration of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal injection of SB203580, a conventional and well-characterized inhibitor, prevents knee joint neutrophil recruitment, edema formation, experimental score and cytokine production. This local anti-inflammatory effect was completely abolished with chemical sympathectomy (guanethidine) and beta-adrenergic receptors blockade (nadolol). In conclusion, our results suggest that pharmacological strategies involving the modulation of spinal p38 MAPK circuit can prevent joint inflammation via sympathetic networks and beta-adrenoceptors activation. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/04237-2 - Via Colinérgica Anti-inflamatória: O papel da neuroimunomodulação no controle da resposta Inflamatória.
• Beneficiário: Alexandre Kanashiro
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 11/20343-4 - Via colinérgica anti-inflamatória: o papel da neuroimunomodulação no controle da resposta inflamatória
• Beneficiário: Alexandre Kanashiro
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores