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Hypoxia Attenuates Colonic Innate Immune Response and Inhibits TLR4/NF-κB Signaling Pathway in Lipopolysaccharide-Induced Colonic Epithelial Injury Mice.
- Source :
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Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research [J Interferon Cytokine Res] 2023 Jan; Vol. 43 (1), pp. 43-52. Date of Electronic Publication: 2023 Jan 05. - Publication Year :
- 2023
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Abstract
- High altitude hypoxia can lead to a spectrum of gastrointestinal problems. As the first line of host immune defense, innate immune response in the intestinal mucosa plays a pivotal role in maintaining intestinal homeostasis and protecting against intestinal injury at high altitude. This study aimed to investigate the effect of hypoxia on the colonic mucosal barrier and toll-like receptor 4 (TLR4)-mediated innate immune responses in the colon. The mice were exposed to a hypobaric chamber to simulate a 5,000 m plateau environment for 7 days, and the colonic mucosa changes were recorded. At the same time, the inflammation model was established by lipopolysaccharide (LPS) to explore the effects of hypoxia on the TLR4/nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ] in the colon. We found that hypoxic exposure caused weight loss and structural disturbance of the colonic mucosa in mice. Compared with the control group, the protein levels of TLR4 [fold change (FC) = 0.75 versus FC = 0.23], MyD88 (FC = 0.80 versus FC = 0.30), TIR-domain-containing adaptor protein inducing interferon-β (TRIF: FC = 0.89 versus FC = 0.38), and NF-κB p65 (FC = 0.75 versus FC = 0.24) in the colon of mice in the hypobaric hypoxia group were significantly decreased. LPS-induced upregulation of the TLR4/NF-κB signaling and its downstream inflammatory factors was inhibited by hypoxia. Specifically, compared with the LPS group, the protein levels of TLR4 (FC = 1.18, FC = 0.86), MyD88 (FC = 1.20, FC = 0.80), TRIF (FC = 1.20, FC = 0.86), and NF-κB p65 (FC = 1.29, FC = 0.62) and the mRNA levels of IL-1β (FC = 7.38, FC = 5.06), IL-6 (FC = 16.06, FC = 9.22), and IFN-γ (FC = 2.01, FC = 1.16) were reduced in the hypobaric hypoxia plus LPS group. Our findings imply that hypoxia could lead to marked damage of the colonic mucosa and a reduction of TLR4-mediated colonic innate immune responses, potentially reducing host defense responses to colonic pathogens.
- Subjects :
- Animals
Mice
Adaptor Proteins, Vesicular Transport genetics
Adaptor Proteins, Vesicular Transport metabolism
Adaptor Proteins, Vesicular Transport pharmacology
Colon immunology
Colon pathology
Interleukin-6 metabolism
Lipopolysaccharides pharmacology
Myeloid Differentiation Factor 88 metabolism
Signal Transduction
Hypoxia immunology
Hypoxia metabolism
Immunity, Innate
NF-kappa B metabolism
Toll-Like Receptor 4 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7465
- Volume :
- 43
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
- Publication Type :
- Academic Journal
- Accession number :
- 36603105
- Full Text :
- https://doi.org/10.1089/jir.2022.0194