Novel involvement of the immunomodulator AS101 in IL-10 signaling, via the tyrosine kinase Fer

Rami Hayun, Sali Shpungin, Hana Malovani, Michael Albeck, Eitan Okun, Uri Nir, Benjamin Sredni

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

11 Scopus citations

Abstract

Interleukin-10 (IL-10) plays a major proliferative role in many tumors, and activates the transcription factor Stat3 by tyrosine phosphorylation. The immunomodulator ammonium trichloro (dioxoethylene-o,o′) tellurate (AS101) has a direct antitumor activity, and is able to sensitize several tumors to chemotherapy, by inhibiting the tumor IL-10 autocrine loop. The tyrosine kinase Fer is essential for the proliferation of numerous malignant cell lines and in some cases was related to Stat3 activation. This article examined the role of AS101 in IL-10 signaling, and the correlation between Fer and Stat3, in human peripheral blood mononuclear cells (PBMC). We show that Fer was associated with Stat3 in PBMC and RAW 264.7, a macrophage cell line. Recombinant IL-10 (rIL-10) increased the tyrosine phosphorylation of Stat3, upregulated the levels of Fer, and increased the association of Fer with phosphorylated Stat3 (pYStat3). All the activities of IL-10 mentioned above were reversed by AS101. The effects conferred by AS101 were totally abolished by exogenous addition of rIL-10. These results indicate that AS101 downregulates the Stat3 IL-10 loop, and inhibits Fer association with pYStat3. We conclude that anti-IL-10 treatment using AS101, may be beneficial in certain malignancies and other pathologies in which IL-10 secretion is elevated and Stat3 is continuously phosphorylated.

Original languageEnglish
Title of host publicationSignal Transduction Pathways, Part C
Subtitle of host publicationCell Signaling in Health and Disease
PublisherBlackwell Publishing Inc.
Pages240-250
Number of pages11
ISBN (Print)1573316954, 9781573316958
DOIs
StatePublished - Jan 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1095
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • AS101
  • Fer
  • IL-10
  • Mononuclear cell
  • PBMC
  • Stat3
  • Tyrosine kinase

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