{'fraction_non_alphanumeric': 0.04318564217610768, 'fraction_numerical': 0.017386427369601793, 'mean_word_length': 6.281632653061225, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Mast Cell Proteases Activate Glia‐Neurons and Release Interleukin‐33 by Activating MAPKs

Parkinson's disease (PD) is characterized by inflammation‐dependent dopaminergic neurodegeneration in the substantia nigra in the brain. Inflammatory mediators released from activated microglia, astrocytes, neurons, T‐cells and mast cells mediate neuroinflammation and neurodegeneration in the brain. 1‐methyl‐4‐phenylpyridinium (MPP+), a toxic metabolite of the parkinsonian neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induces the release of inflammatory mediators from glial cells, neurons and inflammatory cells including mast cells. Mast cells play an important role in neuroinflammation and neurodegeneration. Mast cell proteases are implicated in neuroinflammation. However, the exact mechanism involved in this process is not yet clearly understood. In the present study, mouse bone marrow‐derived mast cells (BMMCs) and mouse fetal brain‐derived glia/neurons and astrocytes were incubated with MPP+, mouse mast cell protease‐6 (MMCP‐6) and MMCP‐7 in vitro. Inflammatory cytokine interleukin‐33 (IL‐33) released from these cells was quantitated by enzyme‐linked immunosorbent assay. MMCP‐6 or MMCP‐7 stimulates astrocyte and glia/neurons to release significantly more IL‐33 as compared with untreated control cells. MPP+ also induced IL‐33 release from mouse mast cells and glia‐neurons. Our results show that mast cell proteases and MPP+ activate mitogen‐activated protein kinases (MAPKs) p38 and extracellular signal–regulated kinases1/2 (ERK1/2) and release IL‐33 from these cells. We suggest that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD and other neuroinflammatory conditions.