TY - JOUR
T1 - Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2
AU - Fujita, Junya
AU - Mestre, Juan R.
AU - Zeldis, Jerome B.
AU - Subbaramaiah, Kotha
AU - Dannenberg, Andrew J.
PY - 2001
Y1 - 2001
N2 - 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 PGE2 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 PGE2 synthesis. Taken together, these data provide new insights into the antineoplastic and antiinflammatory properties of thalidomide.
AB - 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 PGE2 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 PGE2 synthesis. Taken together, these data provide new insights into the antineoplastic and antiinflammatory properties of thalidomide.
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M3 - Article
C2 - 11705847
AN - SCOPUS:0035186865
SN - 1078-0432
VL - 7
SP - 3349
EP - 3355
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -