Thalidomide and its analogues inhibit lipopolysaccharide-mediated Iinduction of cyclooxygenase-2.
We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induction of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in murine macrophages. Thalidomide caused a dose-dependent inhibition of LPS-mediated 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 with LPS stimulated Cox-2 transcription, an effect that was unaffected by thalidomide. Thalidomide decreased the stability of Cox-2 mRNA. A series of structural 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 anti-inflammatory properties of thalidomide.
Fujita
J
J
Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021, USA.
Mestre
J R
JR
Zeldis
J B
JB
Subbaramaiah
K
K
Dannenberg
A J
AJ
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015151:Immunoblotting; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013792:Thalidomide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases