Multifunctional Activity of a Small Tellurium Redox Immunomodulator Compound, AS101, on Dextran Sodium Sulfate-induced Murine Colitis

Abstract

Background: AS101, a novel small tellurium compound, is a potent anti-inflammatory/anti-apoptotic immunomodulator. Results: AS101 prevents leukocyte migration and protects the mucosal barrier in murine colitis. Conclusion: AS101 exerts multifunctional anti-inflammatory/anti-apoptotic activity in experimental inflammatory bowel diseases. Significance: This is the first report showing significant effect of tellurium-based compound for the treatment of inflammatory bowel diseases.

Sensitizing B- and T- cell Lymphoma Cells to Paclitaxel/Abraxane–Induced Death by AS101 via Inhibition of the VLA-4–IL10–Survivin Axis

“…favorable activities in murine models of autoimmune diseases (35,36). Indeed, we show here that the compound inhibits the activity of VLA-4 on lymphoma cells as expressed by inhibition of cell attachment to the VLA-4 ligand VCAM-1.…”

“…This activity accounted for the conversion of resistant to chemotherapy-sensitive acute myelogenous leukemia cells in vivo (34) and to favorable activities in murine models of autoimmune diseases (35,36). Figure 4A shows that AS101 inhibits the attachment of lymphoma cells to the VLA-4 ligand VCAM-1 in a dose-dependent manner, suggesting inhibition of VLA-4 activity in these cells.…”

The effect of the novel tellurium compound AS101 on autoimmune diseases

“…Moreover, it was recently found that AS101 inhibits LPS-induced IL-6 secretion in macrophages [12] and IL-1β-induced IL-6 secretion in the human retinal pigment epithelium [13] via blocking of the NFκB pathway. Therefore, the inhibition of Th17/IL-17 function and those of associated factors such as IL-6 and IL-1β by AS101 in the inflammatory and autoimmune milieu, as can be seen in experimental IBD [44], EAE [45] and in the lesions of psoriasis patients(unpublished data) demonstrates their clinical importance and suggests a possible mechanism of the anti-autoimmune properties of AS101. While Th17 cells promote autoimmunity, Treg cells serve to control excessive immune responses and therefore play a very important role in autoimmune pathogenesis by maintaining self-tolerance and by controlling expansion and activation of autoreactive CD4 + T effector cells.…”

“…While Th17 cells promote autoimmunity, Treg cells serve to control excessive immune responses and therefore play a very important role in autoimmune pathogenesis by maintaining self-tolerance and by controlling expansion and activation of autoreactive CD4 + T effector cells. As the balance between inflammation (Th17 cells) and tolerance (Treg cells) is critical and may influence pathology or disease outcomes in autoimmune diseases [41], the enhancement of the Treg population by AS101 treatment in the autoimmune environment, as can be seen in experimental IBD [44] and T1D (unpublished data), indicates clinical importance, as well.…”

“…node cells to MAdCAM-1, the α4β7 integrin ligand, was blocked by AS101 treatment both in vitro and in vivo. These results demonstrated the ability of AS101 to inhibit the interaction between α4β7 and MAdCAM-1, and thereby block diapedesis of innate inflammatory effector cells from gut-associated lymphoid tissue or the blood into the colon [44].…”