Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia

• Primary rat astrocytes and microglia were compared for their inflammatory response to acrylonitrile.
• Acrylonitrile upregulates p53 and NF-kB, important mediators of carcinogenesis and inflammation.
• Pro- and anti-inflammatory cytokines and chemokines are differentially affected in the two cells.

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.