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Published on: May 2, 2018
M1 intestinal macrophages-derived exosomes promote colitis progression and mucosal barrier injury
Rui Du1, Sihan Chen1, Chenyang Han2
1College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Aim:
This work aimed to investigate the role of M1 intestinal macrophages-derived exosomes (M1-Exo) in colitis and its mechanism.
Methods:
M1 polarization of intestinal macrophages was induced in vitro, and their exosomes were extracted and identified. Thereafter, the DSS-induced colitis mouse model was built. Each mouse was given intraperitoneal injection of exosomes, and then mouse weight and DAI were dynamically monitored. In addition, the levels of cytokines were detected by ELISA. After treatment with the TLR4 inhibitor Resatorvid, the effects of M1 macrophages-derived exosomes were observed. Besides, the mouse intestinal epithelial cells were cultured in vitro for observing function of M1-Exo.
Results:
M1-exo aggravated the colitis and tissue inflammation in mice, activated the TLR4 signal, and destroyed the mucosal barrier. But M0 macrophages-derived exosomes (M0-Exo) did not have the above effects. Resatorvid treatment antagonized the roles of M1-exo. Moreover, as confirmed by cellular experiments in vitro, M1-exo destroyed mucosal barrier.
Conclusion:
M1-exo serve as the pro-inflammatory mediator, which can promote mouse colitis progression by activating TLR4 signal.
Insights
M1 intestinal macrophages-derived exosomes (M1-Exo) worsen colitis by activating the TLR4 pathway and damaging the gut barrier. M0-Exo did not show these pro-inflammatory effects, indicating M1-Exo
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Intestinal macrophages play a crucial role in maintaining gut homeostasis.
- Dysregulated macrophage polarization is implicated in inflammatory bowel diseases like colitis.
Purpose of the Study:
- To investigate the role of M1 intestinal macrophages-derived exosomes (M1-Exo) in the pathogenesis of colitis.
- To elucidate the underlying mechanism of M1-Exo in exacerbating colitis.
Main Methods:
- M1 polarization of macrophages and exosome extraction in vitro.
- Induction of colitis in a mouse model using DSS, followed by exosome administration.
- Monitoring of disease activity, cytokine levels, and mucosal barrier integrity.
- Inhibition of TLR4 signaling pathway using Resatorvid and assessment of M1-Exo effects.
Main Results:
- M1-Exo significantly aggravated colitis and tissue inflammation in mice.
- M1-Exo activated the TLR4 signaling pathway and compromised the intestinal mucosal barrier.
- Exosomes derived from M0 macrophages (M0-Exo) did not exhibit these pro-inflammatory effects.
- TLR4 inhibition with Resatorvid antagonized the detrimental effects of M1-Exo.
Conclusions:
- M1-Exo act as pro-inflammatory mediators that promote colitis progression.
- Activation of the TLR4 signaling pathway is a key mechanism by which M1-Exo exacerbate colitis.
- Targeting M1-Exo or the TLR4 pathway may offer therapeutic strategies for colitis.
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