Journal Article

Bilberry-Derived Anthocyanins Modulate Cytokine Expression in the Intestine of Patients with Ulcerative Colitis

Zeitz, Jonas, Rogler, Gerhard, Roth, Sofia, Gottier, Claudia, Lang, Silvia, Weber, Achim, Spalinger, Marianne R., Biedermann, Luc, Scharl, Michael

2016

Overview

We previously demonstrated that anthocyanin-rich bilberry extract (ARBE) inhibits IFN-γ-induced signalling and downstream effects in human monocytic cells and ameliorates disease activity in ulcerative colitis (UC) patients. Here, we studied the molecular mechanisms of ARBE-mediated effects in vitro and by analysing colonic tissue and serum samples of UC patients treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial. Colon specimens obtained during an open pilot study using ARBE for the treatment of mild-to-moderate UC were analyzed by immunohistochemistry. Cytokine levels in patients' serum were quantified by ELISA. Cell culture experiments were performed using THP-1 monocytic cells. ARBE treatment inhibited the expression of IFN-γ-receptor 2 in human THP-1 monocytic cells. Colon biopsies of UC patients who responded to the 6-week long ARBE treatment revealed reduced amounts of the pro-inflammatory cytokines IFN-γ and TNF-α. Levels of phosphorylated (activated) p65-NF-κB were reduced in these patients. Further, patients with successful ARBE treatment featured enhanced levels of Th17-cell specific cytokine IL-22 and immunoregulatory cytokine IL-10 as well as reduced serum levels of TNF-α and MCP-1, but enhanced levels of IL-17A, in contrast to patients that did not reach remission after ARBE treatment. Our data suggest a molecular mechanism underlying the anti-inflammatory effects of ARBE treatment in UC patients by modulating T-cell cytokine signalling and inhibiting IFN-γ signal transduction. These data are of particular interest, since ARBE is a promising therapeutic approach for the treatment of IBD.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Anthocyanins / Anthocyanins - pharmacology / Bilberry / Biology and Life Sciences / Biopsy / Cardiovascular disease / Care and treatment / Cell culture / Colitis, Ulcerative - metabolism / Colitis, Ulcerative - pathology / Colon / Crohn's disease / Crohns disease / Cytokines / Cytokines - metabolism / Enzyme-linked immunosorbent assay / Experiments / Female / Flavonoids / Gastroenterology / Gene expression / Health aspects / Helper cells / Hepatology / Hospitals / Humans / Immunohistochemistry / Immunoregulation / Inflammatory bowel disease / Inflammatory bowel diseases / Interleukin 10 / Interleukin 22 / Intestine / Intestines / Lymphocytes T / Male / Medicine and Health Sciences / Molecular modelling / Monocyte chemoattractant protein 1 / Monocytes / NF-κB protein / Pathogenesis / Patients / Phenols / Physiological aspects / Physiology / Polyphenols / Properties / Remission / Rodents / Serum levels / Signal transduction / Signaling / Tissue analysis / Tumor necrosis factor-α / Ulcerative colitis / Vaccinium myrtillus - chemistry / γ-Interferon