Bile acid inhibition of interferon activity in human lymphocytes: no evidence of oxidative stress

Abstract

Cholestasis and bile acids are two factors involved in resistance to interferon therapy in patients with chronic hepatitis C. As bile acids inhibit the biological activity of this cytokine in vitro and are capable of generating oxidative stress in hepatocytes, we investigated the potential involvement of such a mechanism in human lymphocytes. Thus, we evaluated (a) the effects of bile acids (0-200 mumol L-1) on lymphocyte reduced glutathione content and malondialdehyde production and (b) the ability of antioxidants to prevent the inhibitory effect of chenodeoxycholic acid on interferon-induced lymphocyte 2',5'-oligoadenylate synthetase activity, an index of the biological activity of interferon. We found that treatment of lymphocytes with bile acids for 24 h did not induce malondialdehyde release or significantly modify cellular reduced glutathione content. Synthetic precursors of glutathione (N-acetylcysteine and S-adenosylmethionine) and antioxidants (superoxide dismutase and catalase) had no preventive influence on the inhibitory effect of chenodeoxycholic acid on interferon-induced 2',5'-oligoadenylate synthetase activity. These negative results do not provide evidence for the use of glutathione precursors in cholestatic conditions associated with viral diseases.

Bile acids PKA-dependently induce a switch of the IL-10/IL-12 ratio and reduce proinflammatory capability of human macrophages

“…Thereby, bile acids have been shown to affect the function of cytokine-driven effector mechanisms of innate immunity, as well as the function of cells of innate and adaptive immunity, including monocytes, macrophages, NK cells, and T cells. Hence, bile acids affect intracellular signaling in response to type I IFNs or cytokines, such as IL-6, and subsequent gene expression in immune cells, such as NK cells or lymphocytes, as well as in epithelial cells, such as hepatocytes [11][12][13][14][15]. Moreover, bile acids alter the primary humoral response in human monocytes by inhibition of cell proliferation and exocytosis of Ig [16], and a variety of different reports indicates that they substantially impair macrophage functions, including phagocytic activity, as well as production of the cytokines TNF-␣ or IL-6, in response to inflammatory stimuli, such as LPS [17][18][19][20].…”

Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells

“…In earlier reports, bile acids have been shown to counteract IFN pathways in liver cells and natural killer cells (24)(25)(26). Podevin et al showed that bile acids inhibited IFN-induced 2Ј,5Ј oligoadenylate synthetase (OAS) activity in different hepatoma cell lines, including Huh-7 (26).…”