J Cancer Prev.  2020 Jun;25(2):119-125. 10.15430/JCP.2020.25.2.119.

Anti-colonic Inflammation by Black Raspberries through Regulating Toll-like Receptor-4 Signaling in Interlukin-10 Knockout Mice

Affiliations
  • 1Department of Obstetrics and Gynecology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
  • 2Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
  • 3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • 4Division of Biostatistics, Department of Science of Informatics, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA
  • 5Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
  • 6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, with a steadily rising prevalence in Western and newly industrialized countries. UC patients have a cancer incidence as high as 10% after 20 years of the disease. Although the importance of fruits and vegetables in defense against UC is beginning to be appreciated, the mechanisms remain largely unclear. In the current study, we reported that dietary black raspberries (BRBs) decreased colonic inflammation in the mucosa and submucosa of interleukin (IL)-10 knockout (KO) mice. We then used colon, spleen, and plasma from those mice to investigate whether BRBs exert their anti-inflammatory effects by correcting dysregulated toll-like receptor (TLR)-4 signaling to downregulate prostaglandin E2 (PGE2). Other studies reported that spleen is the reservoir of macrophages and depletion of macrophages in IL-10 KO mice prevents the development of colitis. Our results showed that BRBs decreased the percentages of macrophages in spleens of IL-10 KO mice. Moreover, mechanistically, the BRB diet corrected dysregulated TLR-4 signaling in cells from the colon and spleen, decreased PGE2 and prostaglandin I2, and increased 15-lipoxygenase and its product, 13-S-hydroxyoctadecadienoic acid, in plasma of IL- 10 KO mice. Therefore, we have elucidated one of the anti-inflammatory mechanisms of BRBs, and have identified biomarkers that could be indicators of response in UC patients treated with them. Our findings with BRBs could well apply to many other commonly consumed fruits and vegetables.

Keyword

Ulcerative colitis; Black raspberries; Toll-like receptor-4 pathway; Spleen; interleukin-10 knockout mice
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