Mast Cell Proteases Activate Astrocytes and Glia-Neurons and Release Interleukin-33 by Activating p38 and ERK1/2 MAPKs and NF-κB

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Inflammatory mediators released from activated microglia, astrocytes, neurons and mast cells mediate neuroinflammation. Parkinson’s disease (PD) is characterized by inflammation-dependent dopaminergic neurodegeneration in substantia nigra. 1-methyl-4-phenylpyridinium (MPP + ), a metabolite of parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induces inflammatory mediators release from brain cells and mast cells. Brain cells interaction with mast cells are implicated in neuroinflammation. However, the exact mechanism involved are not yet clearly understood. Mouse fetal brain-derived cultured primary astrocytes and glia-neurons were incubated with mouse mast cell protease-6 (MMCP-6) and MMCP-7, and mouse bone marrow-derived mast cells (BMMCs) were incubated with MPP + and brain protein glia maturation factor (GMF). Interleukin-33 (IL-33) released from these cells was quantitated by enzyme-linked immunosorbent assay. Both MMCP-6 and MMCP-7-induced IL-33 release from astrocytes and glia-neurons. MPP + and GMF used as a positive control-induced IL-33 and reactive oxygen species expression in mast cells. Mast cell proteases and MPP + activate p38 and extracellular signal-regulated kinases 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs) and transcription factor nuclear factor-kappa B (NF-κB) in astrocytes, glia-neurons or mast cells. Addition of BMMCs from wt mice and transduction with adeno-GMF show higher chemokine (C-C motif) ligand 2 (CCL2) release. MPP + activated glial cells, and reduced microtubule associated protein 2 (MAP-2) expression indicating neurodegeneration. IL-33 expression increased in the midbrain and striatum of PD brains as compared with age and sex matched control subjects. Glial cells and neurons interact with mast cells and accelerate neuroinflammation and these interactions can be explored as a new therapeutic target to treat PD.

Related collections

Most cited references 62

Record: found
Abstract: found
Article: not found

The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury.

Sachin Gadani, James Walsh, Igor Smirnov … (2015)

Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 have impaired recovery after CNS injury, which is associated with reduced myeloid cell infiltrates and decreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment to the injured CNS and may lead to new therapeutic insights in CNS injury and neurodegenerative diseases.

0 comments Cited 166 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Role of neuroinflammation in neurodegeneration: new insights

Róisín McManus, Michael T Heneka (2017)

Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, the past 15 years have established a key role for infectious pathogens in the progression of age-related neurodegeneration. It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer’s disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. This can occur from typical infectious challenges such as respiratory tract infections, although a number of specific viral, bacterial, and fungal pathogens have also been associated with the development of the disease. To date, it is not clear whether these microorganisms are directly related to Alzheimer’s disease progression or if they are opportune pathogens that easily colonize those with dementia and exacerbate the ongoing inflammation observed in these individuals. This review will discuss the impact of each of these challenges, and examine the changes known to occur with age in the peripheral immune system, which may contribute to the age-related vulnerability to infection-induced cognitive decline.

0 comments Cited 113 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mast cells in neuroinflammation and brain disorders.

Erik Hendriksen, Doris van Bergeijk, Ronald Oosting … (2017)

It is well recognized that neuroinflammation is involved in the pathogenesis of various neurodegenerative diseases. Microglia and astrocytes are major pathogenic components within this process and known to respond to proinflammatory mediators released from immune cells such as mast cells. Mast cells reside in the brain and are an important source of inflammatory molecules. Mast cell interactions with glial cells and neurons result in the release of mediators such as cytokines, proteases and reactive oxygen species. During neuroinflammation, excessive levels of these mediators can influence neurogenesis, neurodegeneration and blood-brain barrier (BBB) permeability. Mast cells are considered first responders and are able to initiate and magnify immune responses in the brain. Their possible role in neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease and autism has gained increasing interest. We discuss the possible involvement of mast cells and their mediators in neurogenesis, neurodegeneration and BBB permeability and their role in neuronal disorders such as cerebral ischemia, traumatic brain injury, neuropathic pain, multiple sclerosis, Alzheimer's disease, migraine, autism, and depression.