Three Important Short-chain Fatty Acids (SCFAs) Attenuate the Inflammatory Response Induced by 5-FU and Maintain the Integrity of Intestinal Mucosal Tight Junction

Overview

Journal BMC Immunol

Publisher Biomed Central

Specialty Allergy & Immunology

Date 2022 Apr 22

PMID 35448938

Authors

Xi Yue

Sun Wen

Ding Long-Kun

Yan Man

Sun Chang

Zhang Min

Li Shuang-Yu

Qian Xin

Ma Jie

Wu Liang

Affiliations

Soon will be listed here.

Abstract

Background: 5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear.

Results: To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1β, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1β, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased.

Conclusions: These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

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