Deciphering the In vitro Role of microRNAs miR-21-3p and miR-222-5p In the Regulation of Clostridioides difficile Flagellin-Induced Inflammation
Clostridioides difficile infection (CDI) induces severe intestinal inflammation, mediated partly by the NF-κB signaling pathway. Flagellin (FliC), a major component of C. difficile flagella, plays a pivotal role in host-pathogen interactions by inducing inflammation via Toll-like receptor 5 (TLR5)....
محفوظ في:
| المؤلف الرئيسي: | |
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| التنسيق: | masterThesis |
| منشور في: |
2024
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/16713 https://doi.org/10.26756/th.2023.772 http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php |
| الوسوم: |
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| الملخص: | Clostridioides difficile infection (CDI) induces severe intestinal inflammation, mediated partly by the NF-κB signaling pathway. Flagellin (FliC), a major component of C. difficile flagella, plays a pivotal role in host-pathogen interactions by inducing inflammation via Toll-like receptor 5 (TLR5). MicroRNAs (miRNAs) are critical regulators of inflammation and may serve as therapeutic targets. While prior studies demonstrated the anti-inflammatory role of miR-27a-5p in FliC-induced inflammation, the roles of miR-222-5p and miR-21-3p remain unclear. This study aimed to elucidate the regulatory roles of these miRNAs in FliC-induced inflammatory responses in intestinal epithelial cells. Preliminary analysis of stool samples from CDI patients revealed an upregulation of miR-222-5p and miR-21-3p. Quantitative PCR revealed that FliC stimulation upregulated miR-222-5p and miR-21-3p expression within 2 hours of treatment. Functional assays revealed that miR-222-5p overexpression led to a significant increased expression of key pro-inflammatory cytokines, including IL-8 and TNF-α, while knockdown of these miRNAs resulted in their decreased expression. Western blot and pathway analyses demonstrated that miR-222-5p and miR-21-3p overexpression increased phosphorylation of p65, a key component of the NF-κB complex, while their knockdown reduced p65 phosphorylation. Preliminary data suggest that for miR-222-5p, this effect may occur through downregulating NF-κB repressing factor (NKRF), leading to enhanced NF-κB activation, highlighting the pro-inflammatory roles of these miRNAs. These findings underscore the roles of miR-222-5p and miR-21-3p as potential regulators of FliC-induced inflammation and provide insight into the molecular mechanisms underlying C. difficile-associated inflammatory responses. Future studies could explore their therapeutic potential in mitigating intestinal inflammation in vivo in mouse model of C. difficile infections. |
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