Thalidomide inhibits interferon-γ-mediated nitric oxide production in mouse vascular endothelial cells

Battuvshin Badamtseren, Erdenezaya Odkhuu, Naoki Koide, Abedul Haque, Yoshikazu Naiki, Shoji Hashimoto, Takayuki Komatsu, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Thalidomide is known as an anti-angiogenic, anti-tumor, and anti-proliferative agent, widely used in the treatment of some immunological disorders and cancers. The effect of thalidomide on interferon (IFN)-γ induced nitric oxide (NO) production in mouse vascular endothelial cells was examined in order to elucidate the anti-angiogenic or anti-inflammatory action. Thalidomide inhibited IFN-γ-induced NO production in mouse END-D cells via reduced expression of an inducible type of NO synthase (iNOS) protein and mRNA. Since thalidomide did not alter the cell surface expression of IFN-γ receptor, the NO inhibition was suggested to be due to the impairment of IFN-γ-induced intracellular event by thalidomide. Thalidomide inhibited the phosphorylation of IRF1, which was required for the iNOS expression. Moreover, it inhibited the phosphorylation of STAT1, an upstream molecule of IRF1, in IFN-γ signaling. Thalidomide did not inhibit the JAK activation in response to IFN-γ. A phosphatase inhibitor, sodium orthovanadate, abolished the inhibitory action of thalidomide. Therefore, thalidomide was suggested to inhibit IFN-γ-induced NO production via impaired STAT1 phosphorylation.

Original languageEnglish
Pages (from-to)19-24
Number of pages6
JournalCellular Immunology
Volume270
Issue number1
DOIs
Publication statusPublished - 07-04-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology

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