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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: FUNDAMENTAL & CLINICAL PHARMACOLOGY; v. 32, n. 2, p. 155-162, APR 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/04237-2 - Antiinflammatory Cholinergic Pathway: The role of neuroimmunomodulation in the control of inflammatory response.
• Grantee: Alexandre Kanashiro
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response
• Grantee: Alexandre Kanashiro
• Support Opportunities: Research Grants - Young Investigators Grants