Cytomegalovirus Infection Exacerbates Experimental Colitis by Promoting IL-23 Production
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Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.
KEY WORDScytomegalovirus colitis IL-23 NF-κB
Dulbecco’s modified Eagle’s medium
Dextran sodium sulfate
Fetal bovine serum
Inflammatory bowel disease
Mouse embryo fibroblast cells
Specific pathogen free
Lingling Xuan designed and performed the experiments, analyzed the data, and drafted the manuscript. Lulu Ren assisted in in vivo experiments and revised the manuscript. Feifei Han and Lili Gong assisted in MCMV propagation. Zirui Wan, Song Yang, and He Liu helped in the analysis of data. Yali Lv and Lihong Liu designed the study, drafted and revised the manuscript. All authors read and approved the final manuscript.
This study was supported by Scientific Research Foundation of Capital Medical University (Nos. PYZ2018030 and 3500-1182080843), and National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (No. 2017ZX09101001, Beijing, China).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All of the animal experiments followed the instructions of the Laboratory Animal Management Statute of China Physiological Society and were approved by the Beijing Chao-Yang Hospital Committee on Ethics in the Care and Use of Laboratory Animals.
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