Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2

We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induct ion of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in muri ne macrophages. Thalidomide caused a dose-dependent inhibition of LPS-media ted induction of PGE(2) synthesis in RAW 264.7 cells. The induction of Cox- 2 protein and mRNA by LPS was also suppressed by thalidomide. Based on the results of nuclear run-off assays and transient transfections, treatment wi th LPS stimulated Cox-2 transcription, an effect that was unaffected by tha lidomide. Thalidomide decreased the stability of Cox-2 mRNA. A series of st ructural analogues of thalidomide also inhibited LPS-mediated induction of Cox-2 and PGE(2) synthesis. Taken together, these data provide new insights into the antineoplastic and antiinflammatory properties of thalidomide.