Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kanashiro, A; Franchin, M; Bassi, GS; Reis Santana, DA; Cunha, TM; Cunha, FQ; Ulloa, L; Rodrigues, GJ
Published Date
- April 2018
Published In
Volume / Issue
- 32 / 2
Start / End Page
- 155 - 162
PubMed ID
- 29206314
Pubmed Central ID
- PMC6262227
Electronic International Standard Serial Number (EISSN)
- 1472-8206
Digital Object Identifier (DOI)
- 10.1111/fcp.12338
Language
- eng
Conference Location
- England