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Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines
Dorina Lauritano1, Filiberto Mastrangelo2, Cristian D'Ovidio3
1Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.
Abstract:
Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.
Insights
Mast cells (MCs) play a crucial role in brain inflammation and nervous system disorders by releasing inflammatory mediators. Targeting MC activation with anti-inflammatory cytokines like IL-37 and IL-38 may offer therapeutic benefits.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Immunology
Background:
- Mast cells (MCs) are immune cells originating from bone marrow stem cells.
- MCs contribute to allergic reactions, inflammation, immunity, autoimmunity, and mental disorders.
- MCs in the brain interact with microglia and neurons, influencing CNS pathology.
Purpose of the Study:
- To explore the current understanding of Mast cell activation in the central nervous system.
- To investigate the role of neuropeptides and pro-inflammatory cytokines in MC-mediated CNS disorders.
- To suggest potential therapeutic strategies involving anti-inflammatory cytokines.
Main Methods:
- Review of scientific literature on Mast cells and nervous system diseases.
- Analysis of MC interactions with microglia and neurons.
- Examination of MC activation pathways involving neuropeptides (Substance P, CRH, neurotensin) and cytokines (TNF, IL-1, IL-6).
Main Results:
- MCs release inflammatory mediators like histamine, tryptase, IL-1, IL-6, and TNF.
- MCs store and release tumor necrosis factor (TNF), an inflammatory cytokine.
- Neuropeptides such as Substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin activate MCs, leading to CNS inflammation.
- MCs interact with neurons, causing excitation and releasing inflammatory mediators.
Conclusions:
- Mast cell activation by neuropeptides and pro-inflammatory cytokines contributes to central nervous system inflammatory disorders.
- Further research into human studies is needed, as much current data is from animal models.
- Anti-inflammatory cytokines Interleukin-37 (IL-37) and Interleukin-38 (IL-38) show potential as therapeutic agents for CNS inflammatory conditions mediated by Mast cells.
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