Dilinoleoylphosphatidylcholine decreases hepatic stellate cell activation

The prevention of cirrhosis in alcohol-fed baboons by the administration of a soybean extract-43% to 50% of which was dilinoleoyl-phosphatidylcholine (DLPC) and 24% of which was 1,palmitoyl 2,linoleoyl-phosphatidylcholine (PL PC)-was associated with a significant reduction in the number of stellate c ells transformed to myofibroblast-like cells. To study whether these two ma jor phospholipids affect the similar transformation that occurs by culturin g stellate cells on uncoated plastic, we assessed their effects on prolifer ation (by (methyl-H-3)-thymidine incorporation into DNA), expression of a-s mooth muscle actin and type I procollagen (by densitometry of Western blots ), and collagen synthesis (by incorporation of tritiated proline into colla genase-digestible proteins). These manifestations of stellate cell activati on were decreased by 10 mu mol/L DLPC but not by in mu mol/L PLPC when comp ared with controls incubated either with 17 mmol/L ethanol (used as solvent for the phospholipids) or without addition. These agents did not affect ce ll viability, contamination with other cells, or the capacity of stellate c ells to synthesize protein. Thus DLPC specifically decreases the in vitro a ctivation of stellate cells, as judged by the decreases in proliferative ac tivity, a-smooth muscle actin and procollagen I expressions, and collagen s ynthesis, whereas PLPC did not show such effects. alpha(1)-Procollagen (typ e I) mRNA was not affected by DLPC, suggesting a posttranslational effect. The reduction in the activation of hepatic stellate cells by DLPC may be re sponsible for, or at least contribute to, the prevention of fibrosis by the polyenylphosphatidylcholine mixture administered in vivo.