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

Junya Fujita; Juan R. Mestre; Jerome B. Zeldis; Kotha Subbaramaiah; Andrew J. Dannenberg

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

Junya Fujita, Juan R. Mestre, Jerome B. Zeldis, Kotha Subbaramaiah, Andrew J. Dannenberg

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	3349-3355
Number of pages	7
Journal	Clinical Cancer Research
Volume	7
Issue number	11
State	Published - 2001

ASJC Scopus subject areas

General Medicine

Cite this

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title = "Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2",

abstract = "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.",

author = "Junya Fujita and Mestre, \{Juan R.\} and Zeldis, \{Jerome B.\} and Kotha Subbaramaiah and Dannenberg, \{Andrew J.\}",

year = "2001",

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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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JF - Clinical Cancer Research

IS - 11

ER -

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

Abstract

ASJC Scopus subject areas

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