Delta-9-tetrahydrocannabinol: an inhibitor of STAT1 alpha protein tyrosine phosphorylation

Tyrosine-phosphorylated signal transducer and activator of transcription 1 alpha (STAT1 alpha) is a 91-kDa protein responsible for interferon-gamma (IFN-gamma)-dependent transcription. The present study demonstrates that activation by IFN-gamma of murine macrophages resulted in tyrosine phosphorylation of STAT1 alpha identified by immunoprecipitation. The tyrosine phosphorylation of STAT1 alpha was found highly sensitive to treatment by delta-9 tetrahydrocannabinol (THC), a major marijuana component. Subsequently, the isoform formation of p91 due to tyrosine phosphorylation was reduced in THC-treated macrophages. Although inhibition by THC of the tyrosine phosphorylation of STAT1 alpha induced by IFN-gamma was in a THC concentration-related manner, the tyrosine phosphorylation of other proteins induced by lipopolysaccharide/IFN-gamma treatment of macrophages appeared insensitive to THC treatment. Our data suggest that blockade by THC of tyrosine phosphorylation of STAT1 alpha may be an important mechanism involved in the broad immunosuppressive effects of THC.