Role of TLR4/NF-κB in Damage to Intestinal Mucosa Barrier Function and Bacterial Translocation in Rats Exposed to Hypoxia
Open accessAbstract
The role of Toll-like receptor 4 (TLR4)/nuclear factor-kappa-B (NF-κB) in intestinal mucosal barrier damage and bacterial translocation under hypoxic exposure is unclear. Here, we investigated their role using an acute hypobaric hypoxia model. Adult Sprague-Dawley rats were divided into control (C), hypoxia (H), hypoxia+NF-κB inhibitor pyrrolidinedithiocarbamic acid (PDTC) (100 mg. kg) (HP), hypoxia+0.5 mg/kg lipopolysaccharide (HPL), and hypoxia+PDTC+LPS (HPL) group. Except control group, other four groups were placed in a hypobaric chamber set at 7000 m. Samples were collected at 72 h after pressure reduction. Damage in ultrastructure of the intestinal tract was examined by transmission electron microscopy and bacterial translocation was detected by cultivation. Kinetic turbidimetric assay was used to measure the serum LPS.ELISA was performed to detect TNF-α and IL-6 serum concentrations. Fluorescent quantitative RT-PCR was used to measure TLR4 mRNA levels was measured using quantitative RT-PCR and protein of NF-κB p65 was measured by western blotting. Different degrees of intestinal mucosa damage were observed in groups H and HL. The damage was significantly alleviated after blockage of the TLR4/NF-κB signaling pathway. PDTC- treatment also reversed hyoxia- and LPS-induced bacterial translocation rate and increased serum levels of LPS, TNF-α, and IL-6. TLR4 mRNA levels and NF-κB p65 expression were consistent with the serum factor results. This study suggested that TLR4 and NF-κB expression increased in rat intestinal tissues after acute hypoxia exposure. PDTC-treatment reversed TLR4 and NF-κB upregulation and alleviated damage to the intestinal tract and bacterial translocation. Thus, the TLR4/NF-κB signaling pathway may be critical to the mechanism underlying hypoxia-induced damage to intestinal barrier function and bacterial translocation.
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The TLR4/NF-κB signaling pathway may be critical to the mechanism underlying hypoxia-induced damage to intestinal barrier function and bacterial translocation.
“It was also shown that the TLR4/NF-κB signaling pathway may be critical to the mechanism underlying hypoxia-induced damage to intestinal barrier function and bacterial translocation.161”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [161]
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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- Authors
- Luo, H., Guo, P., & Zhou, Q.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Zhou, Qiquan
- ORCID
- Luo, Han
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-10-17
- Volume
- 7
- Issue
- 10
- Pages
- e46291
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3474812
- OpenAlex
- W1982834823
- Cited by
- 82
- References
- 35
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 4 · 2014: 4
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese People’s Liberation Army
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- TLR4, NF-κB signaling, hypobaric hypoxia, intestinal barrier, bacterial translocation, lipopolysaccharide, TNF-α, interleukin-6, NF-κB p65
- MeSH terms
- Animals, Hypoxia, Bacteria, Capillaries, Fluorescence, Gene Expression Regulation, Intestinal Mucosa, Lipopolysaccharides, Male, Movement, RNA, Messenger, Tumor Necrosis Factor-alpha, Blotting, Western, Interleukin-6, Rats, Sprague-Dawley, Toll-Like Receptor 4, Rats, Transcription Factor RelA, Real-Time Polymerase Chain Reaction, Occludin
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