Presence of cell-free DNA (cfDNA) in sera of patients with inflammatory bowel diseases (IBD) is a long-known fact. The biological effect of cfDNA administration on cellular autophagy within normal and inflammatory circumstances remains unclear. In this study, the effects of intravenous cfDNA pretreatment on autophagy response were studied in dextran sulfate sodium (DSS)-induced acute experimental colitis. Selected proinflammatory cytokine and autophagy-related gene and protein expressions were compared with clinical and histological activity parameters, and with transmission electron microscopic evaluations. A single intravenous dose of cfDNA pretreatment with cfDNA from colitis exhibited beneficial response concerning the clinical and histological severity of DSS-colitis as compared with effects of normal cfDNA. Pretreatment with colitis-derived cfDNA substantially altered the gene and protein expression of several autophagy and inflammatory cytokine genes in a clinically favorable manner. Autophagy in splenocytes is also altered after colitis-derived cfDNA pretreatment. During the process of acute colitis, the subsequent inflammatory environment presumably results in changes of cfDNA with the potential to facilitate cell protective autophagy. Understanding the molecular mechanisms behind the impact of colitis-associated autophagy, and elucidating alterations of the interaction between autophagy and innate immunity caused by nucleic acids may provide further insight into the etiology of IBD. By targeting or modifying cfDNA, novel anti-inflammatory therapies may be developed.
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MC and FS contributed equally.
Contributors All authors have contributed to study organizing, performing research, evaluating, writing and editing.
Funding The study was funded by the StartUp Program of Semmelweis University Faculty of Medicine (CO No.: 11720, Ikt.sz.: 5127/AOKGIE/2018; SE10332470).
Disclaimer The funders had no role in data collection, decision to publish or preparation of the manuscript.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The experimental protocol was approved by the Ethics Committee of Animal Welfare of the Medical Faculty of Semmelweis University (No.: 22.1/1159/3/2010).
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.