ArticleCell death & disease2021
Synergistic effect of the TLR5 agonist CBLB502 and its downstream effector IL-22 against liver injury.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Frontiers in immunology · 2026Review
- Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5.Gut microbes · 2025Article
- Targeting immunosenescence and inflammaging: advancing longevity research.Experimental & molecular medicine · 2025Review
- The Impact of Toll-Like Receptor 5 on Liver Function in Age-Related Metabolic Disorders.Aging cell · 2025Article
- IL-22, a vital cytokine in autoimmune diseases.Clinical and experimental immunology · 2024Review
- TLR5 agonists enhance anti-tumor immunity and overcome resistance to immune checkpoint therapy.Communications biology · 2023Article
- The research development of STAT3 in hepatic ischemia-reperfusion injury.Frontiers in immunology · 2023Review
- Toll-like Receptor Mediation in SARS-CoV-2: A Therapeutic Approach.International journal of molecular sciences · 2022Review
- Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.Pharmaceutics · 2022Review
- Toll-like Receptor Agonist CBLB502 Protects Against Radiation-induced Intestinal Injury in Mice.In vivo (Athens, Greece)Article
- Toll-like Receptor Agonist CBLB502 Protects Against Cisplatin-induced Liver and Kidney Damage in Mice.In vivo (Athens, Greece)Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The toll-like receptor 5 (TLR5) agonist, CBLB502/Entolimod, is a peptide derived from bacterial flagellin and has been shown to protect against radiation-induced tissue damage in animal models. Here we investigated the protective mechanism of CBLB502 in the liver using models of ischemia-reperfusion injury and concanavalin A (ConA) induced immuno-hepatitis. We report that pretreatment of mice with CBLB502 provoked a concomitant activation of NF-κB and STAT3 signaling in the liver and reduced hepatic damage in both models. To understand the underlying mechanism, we screened for cytokines in the serum of CBLB502 treated animals and detected high levels of IL-22. There was no transcriptional upregulation of IL-22 in the liver, rather it was found in extrahepatic tissues, mainly the colon, mesenteric lymph nodes (MLN), and spleen. RNA-seq analysis on isolated hepatocytes demonstrated that the concomitant activation of NF-κB signaling by CBLB502 and STAT3 signaling by IL-22 produced a synergistic cytoprotective transcriptional signature. In IL-22 knockout mice, the loss of IL-22 resulted in a decrease of hepatic STAT3 activation, a reduction in the cytoprotective signature, and a loss of hepatoprotection following ischemia-reperfusion-induced liver injury. Taken together, these findings suggest that CBLB502 protects the liver by increasing hepatocyte resistance to acute liver injury through the cooperation of TLR5-NF-κB and IL-22-STAT3 signaling pathways.
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