Indoxyl 3-sulfate stimulates Th17 differentiation enhancing phosphorylation of c-Src and STAT3 to worsen experimental autoimmune encephalomyelitis

Toward Understanding the Role of Aryl Hydrocarbon Receptor in the Immune System: Current Progress and Future Trends

“…Similar results are observed when EAE mice are treated with nanoparticles carrying ITE and MOG 35–55 [127]. Conversely, treating mice with FICZ or indoxyl 3-sulfate (I3S) worsens EAE, which is likely attributed to the prompted Th17 differentiation [13, 128]. Interestingly, while systematic injection of FICZ does not affect EAE development, local application of FICZ enhances the development of Th17 cells and exacerbates autoimmune conditions [44].…”

Cyclic stretch-induced TGF-β1 and fibronectin expression is mediated by β1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells

“…These results show that STAT3 is involved in stretch-induced fibronectin and TGF-␤1 expression and that stretch-stimulated fibronectin expression in HK-2 cells was mediated by TGF-␤1. (11,24,50) and fibronectin (2,59,60). Moreover, previous studies from this laboratory have shown that mechanical stretch activates c-Src in renal tubular cells (1).…”

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

“…At present, kynurenine, kynurenic acid, indoleacetic acid, and indoxyl sulfate-all indolic products of tryptophan metabolism-have been shown to bind to the AhR or induce the expression of AhR response genes, such as CYP1A1. 38,[93][94][95][96][97] Moreover, as shown in Table 3, all four metabolites activate the AhR at concentrations either similar to the highest C max determined in dialysis patients (eg, indole acetic acid) or at levels decisively lower than the C max , for instance indoxyl sulfate. To date, the clinical implications of AhR activation in the setting of CKD development and progression remain unclear, however, it has been postulated that uremic solutes might evoke dioxinlike toxicity, 38 leading to suppression of immune responses, induction of carcinogenesis and accelerating tumor growth, and promoting atherosclerosis.…”