title: Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia.
abstract: Acrylonitrile (ACN) is extensively used in the production of plastics, resins, nitriles and other commercial products. Chronic low dose exposures to ACN cause glial cell tumors in rats, primarily microglial in origin. Recently it has been determined that astrocytes and microglia respond to ACN-induced oxidative stress differently, which may influence cell-specific activation of inflammatory and carcinogenic pathways. This study was conducted to compare the inflammatory responses of astrocytes and microglia following ACN treatment in vitro to further characterize differential sensitivities and adaptive responses in these cell types. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 levels were measured along with levels of 12 different cytokines and chemokines in primary rat microglia and astrocytes. Additionally levels of cytochrome P450 2E1 (CYP2E1) were measured to evaluate the cells' ability to metabolize ACN. Results indicate that while both cells upregulate p53 and NF-κB, the cytokines and chemokines produced differ between the cell types. Astrocytes, but not microglia, upregulated CYP2E1 in response to ACN, which may be due to the astrocytes accumulating more ACN than the microglia. Altogether our data implicate the inflammatory response as an important event in ACN-induced neurotoxicity.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Caito
authors.affiliation: Division of Clinical Pharmacology and Pediatric Toxicology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address: michael.aschner@einstein.yu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000181:Acrylonitrile / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D019392:Cytochrome P-450 CYP2E1; D000181:Acrylonitrile
keywords: Acrylonitrile; Astrocytes; Inflammation; Microglia; NF-κB; p53