ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Pooled it
- Identification and characterization of a lipopolysaccharide binding, anti-inflammatory protein fromGut microbes · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives.Molecular biomedicine · 2026Review
- Cardiovascular risk in inflammatory bowel disease: focus on lipids and visceral adipose tissue.Frontiers in endocrinology · 2026Review
- Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice.Nature communications · 2024Article
- Toll-like receptor 7 protects against intestinal inflammation and restricts the development of colonic tissue-resident memory CD8Frontiers in immunology · 2024Article
- Investigation of TLR4 Antagonists for Prevention of Intestinal Inflammation.Inflammation · 2023Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021.Frontiers in pharmacology · 2022Review
- BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis.Frontiers in immunology · 2022Article
- TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155.Cell communication and signaling : CCS · 2021Review
- Review
- Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2021Review
- Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6-trinitrobenzenesulfonic acid-induced colitis via repressing toll-like receptor 4/nuclear factor-kappa B.The Kaohsiung journal of medical sciences · 2020Article
- Truncated Pneumolysin fromCells · 2020Article
- Epithelial Toll-like receptors and their role in gut homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2020Review
- Effect of chemical modulation of toll-like receptor 4 in an animal model of ulcerative colitis.European journal of clinical pharmacology · 2020Article
- A Novel Animal Model for Studying Depression Featuring the Induction of the Unfolded Protein Response in Hippocampus.Molecular neurobiology · 2019Article
- TLRs in pulmonary diseases.Life sciences · 2019Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45Rb(hi) T cells into RAG1-/- mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1-/- mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-alpha, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE(2), and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.