CD73 blockade alleviates intestinal inflammatory responses by regulating macrophage differentiation in ulcerative colitis

Wang,Ru; Wang,Yan; Wu,Chao; Jin,Guiyuan; Zhu,Fengqin; Yang,Yonghong; Wang,Yibo; Zhou,Guangxi

doi:10.3892/etm.2023.11972

CD73 blockade alleviates intestinal inflammatory responses by regulating macrophage differentiation in ulcerative colitis

Authors:
- Ru Wang
- Yan Wang
- Chao Wu
- Guiyuan Jin
- Fengqin Zhu
- Yonghong Yang
- Yibo Wang
- Guangxi Zhou
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Affiliations: Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, P.R. China
Published online on: April 21, 2023 https://doi.org/10.3892/etm.2023.11972
Article Number: 272
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by excessive and persistent inflammation. Intestinal macrophages play a considerable role in regulating inflammatory immune reactions in the gut mucosa. It has previously been reported that CD73 is related to the pathogenesis of inflammatory or immune‑related diseases; however, the roles of CD73 in UC remain unclear. In this study, CD73 expression in the inﬂamed mucosa of patients with UC was examined using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting, and immunohistochemistry. Adenosine 5'‑(α, β‑methylene) diphosphate (APCP) was used to block the expression of CD73. Furthermore, the mRNA levels of proinflammatory mediators associated with macrophages following the blocking of CD73 were examined using RT‑qPCR. Finally, the regulatory function of CD73 in intestinal inflammation was assessed by administering APCP in a mouse model of dextran sulfate sodium salt (DSS)‑induced colitis. Notably, it was found that CD73 expression was significantly increased in the colonic mucosal tissues of patients with UC. Blockade of CD73 inhibited the expression of pro-inflammatory cytokines but promoted the production of anti-inflammatory cytokines in macrophages, while its promotion of M2 macrophage polarization was also verified. In vivo, CD73 blockade markedly alleviated DSS‑induced colitis in mice, as characterized by reduced weight loss, reduction in the incidence of diarrhea, and reduced amount of bloody stool. Mechanistically, it was shown that CD73 regulated macrophage differentiation via the NF‑κB and ERK signaling pathways. In conclusion, the findings of the present study indicate that CD73 may have a potential impact on the pathogenesis of UC by modulating the immune response of macrophage differentiation; thus, providing a novel pathway for modulating mucosal inflammation in UC.

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