Differential fibronectin expression in activated C6 glial cells treated with ethanol

The central nervous system is particularly susceptible to alcohol effects a nd toxicity. Glial cells constitute the most common cell type in the brain and play critical roles in normal brain function and during infection and i njury. Astrocytes in particular seem to be important targets for alcohol ne urotoxicity during both development and in adulthood. To gain more insight into alcohol-mediated effects on astrocytes at the molecular level, gene ex pression in rat C6 glial cells was studied in the presence or absence of et hanol. The differential display of mRNA technique was used to screen the ex pressed genes in ethanol-treated rat C6 cells before and after treatment wi th lipopolysaccharide (LPS) combined with phorbol-12-myristate-13-acetate ( PMA), conditions that mimic an infectious inflammatory state and cause immu nologic activation. The present data show that fibronectin appeared as a ma jor gene whose expression is increased in C6 cells by LPS plus PMA stimulat ion and decreased by chronic ethanol exposure, both in mRNA and protein lev els. Fibronectin is a dimeric glycoprotein found in the extracellular matri x of most tissues, in the blood, and on cell surfaces and is involved in ma ny cellular processes. These results show that chronic exposure to ethanol is associated with changes in astrocyte properties during immunologic activ ation that reduce fibronectin expression. The discovery of astrocyte fibron ectin expression as a potential regulated target for chronic alcohol abuse may be useful in understanding, preventing, and treating some brain disorde rs associated with alcohol abuse and alcoholism.