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

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2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalFundamental and Clinical Pharmacology
Volume32
Issue number2
DOIs
StatePublished - Apr 1 2018

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Experimental Arthritis
Neutrophil Infiltration
p38 Mitogen-Activated Protein Kinases
Joints
Chemical Sympathectomy
Nadolol
Inflammation
Guanethidine
Spinal Injections
Zymosan
Receptors, Adrenergic, beta
Knee Joint
Innate Immunity
Adrenergic Receptors
Edema
Spinal Cord
Anti-Inflammatory Agents
Central Nervous System
Phosphorylation
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology

Keywords

  • arthritis
  • beta-adrenergic receptors
  • neuroimmunomodulation
  • neutrophil
  • p38 MAPK
  • sympathetic nervous system

Cite this

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title = "Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation",
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.",
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