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Glia Maturation Factor Stimulates Release of Proinflammatory Mediators from Mast Cells
Author(s) -
Zaheer Asgar,
Kempuraj Duraisamy,
Ramasamy Thangavel,
Zaheer Smita,
Santillan Donna,
Santillan Mark
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb82
Subject(s) - proinflammatory cytokine , neuroinflammation , chemokine , microbiology and biotechnology , tumor necrosis factor alpha , astrocyte , mast cell , biology , chemistry , immunology , inflammation , central nervous system , endocrinology
We have investigated if brain protein glia maturation factor (GMF) and Parkinson's disease (PD)‐relevant toxin 1‐methyl‐4‐phenylpyridinium (MPP+) and α‐synuclein can activate mast cells to release inflammatory mediators. Mast cells are implicated and suggested as a therapeutic target in neuroinflammation but its role in PD is not yet understood. We have analyzed the effect of recombinant GMF, MPP+, α‐synuclein and recombinant IL‐33 on mouse bone marrow‐derived cultured mast cells (BMMCs), human umbilical cord blood‐derived cultured mast cells (hCBMCs), and mouse embryonic brain‐derived cultured astrocytes. The release of cytokines/chemokines was determined by ELISA and the expression of co‐stimulatory molecules CD40 and CD40Ligand by flow cytometry. GMF significantly released chemokine (C‐C motif) ligand 2 (CCL2) from BMMCs when compared to un‐treated control cells. GMF, α‐synuclein and MPP+ activated BMMCs to release interleukin‐1β (IL‐1β), and IL‐8 release from hCBMCs. IL‐33, an IL‐1 family member induced the expression of GMF in human mast cells. GMF induced more tumor necrosis factor‐alpha (TNF‐α) release from astrocyte‐ mast cell co‐culture. Flow cytometry showed increased IL‐33 expression by GMF and MPP+in astrocytes. GMF also induced the expression of CD40 in astrocytes. In conclusion, proinflammatory mediator release from mast cells following GMF, MPP+ or α‐synuclein treatment, and significant release of GMF by mast cells indicate a novel drug target for neurodegenerative diseases including PD.