Premium
Mitoxantrone represses markers of microglial activation and inflammation
Author(s) -
Hensley Lori L.,
Burns Samuel A.,
Chavis Janet A.,
Neal Jeffrey T.,
Ngwanyam Remy R.,
Busby Kelli E.,
Tull Cameron A.,
Drew Paul D.
Publication year - 2006
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.20.5.a879-c
Subject(s) - microglia , mitoxantrone , medicine , astrocyte , multiple sclerosis , inflammation , tumor necrosis factor alpha , neuroprotection , immunology , pharmacology , central nervous system , chemotherapy
Multiple sclerosis (MS) is a neurodegenerative disease characterized by an autoimmune attack against myelin sheaths in the central nervous system (CNS), resulting in unpredictable and varied debilitations, such as temporary blindness, loss of balance, muscle spasticity, incontinence, pain, chronic fatigue, and even paralysis. Mitoxantrone is an FDA‐approved drug used to treat secondary‐progressive forms of the disease, but its mechanism of action is not completely understood, and it has limited use because of cardiotoxicity. This study aimed to determine the effect of mitoxantrone on microglial and astrocyte activation as a measure of the inflammatory response. The results from enzyme‐linked immunosorbent assays (ELISA) and Western blots show that lipopolysaccharide (LPS) stimulates markers of activation, including nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1‐beta (IL‐1β), interleukin‐12 p40 (IL‐12 p40), and monocyte chemoattractant protein‐1 (MCP‐1) in N9 cultured microglia as well as primary astrocytes, and mitoxantrone inhibits these effects in a dose‐dependent manner. The project described was supported by NIH Grant Number P20 RR‐16460 from the IDeA Networks of Biomedical Research Excellence (INBRE) Program of the National Center for Research Resources.