Abstract
Antibiotics are widely used to treat various inflammatory bowel diseases caused by enterotoxigenic Escherichia coli (ETEC). However, continuous use of antibiotics may lead to drug resistance. In this study, we investigated the role of human β-defensin 118 (DEFB118) in regulating the ETEC-induced inflammation and intestinal injury. ETEC-challenged or non-challenged mice were treated by different concentrations of DEFB118. We show that ETEC infection significantly increased fecal score (P < 0.05) and serum concentrations of interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Moreover, the concentrations of D-lactic acid, C-reactive protein (CRP), creatinine (CREA), and urea (P < 0.05) were both increased in the ETEC-challenged mice. However, DEFB118 significantly decreased their concentrations in the serum (P < 0.05). DEFB118 not only alleviated tissue damage in spleen upon ETEC challenge, but also increased the villus height in duodenum and ileum (P < 0.05). Moreover, DEFB118 improved the localization and abundance of tight junction protein ZO-1 in jejunal epithelium. Interestingly, DEFB118 decreased the expression levels of critical genes involving in mucosal inflammatory responses (NF-κB, TLR4, IL-1β, and TNF-α) and the apoptosis (caspase3) upon ETEC challenge (P < 0.05), whereas DEFB118 significantly upregulated the expression of mucosa functional genes such as the mucin1 (MUC1) and sodium-glucose transporter-1 (SGLT-1) in the ETEC-challenged mice (P < 0.05). These results indicated a novel function of the DEFB118. The anti-inflammatory effect of DEFB118 should make it an attractive candidate to prevent various bacteria-induced inflammatory bowel diseases.
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Abbreviations
- ETEC:
-
enterotoxigenic Escherichia coli
- DEFB118:
-
human β-defensin 118
- AMPs:
-
antimicrobial peptides
- HDPs:
-
host defense peptide
- MUC1:
-
mucin1
- MUC2:
-
mucin2
- SGLT-1:
-
sodium-dependent glucose transporter-1
- TLR4:
-
toll-like receptor 4
- NF-κB:
-
nuclear factor-kappa B
- Caspase3:
-
cysteinyl aspartate specific proteinase 3
- Caspase8:
-
cysteinyl aspartate specific proteinase 8
- Caspase9:
-
cysteinyl aspartate specific proteinase 9
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Acknowledgments
We thank Quyuan Wang and Huifen Wang for their assistance during the biochemical analysis.
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This work was supported by the Key Research and Development Program of Sichuan Province (2018NZDZX0005) and the National Natural Science Foundation (31101728).
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QL performed animal trial and prepared the manuscript. XL and QQ F conducted the expression of DEFB118 protein and chemical analysis. JH contributed to experimental design and revised the manuscript. DC, BY, and XM conceived this study and help to manuscript revision. ZH, JY, JL, PZ, and YL contributed to the sample collection and biochemical analysis.
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The animal trial was carried out according to the regulations approved by the Animal Care Committee of Sichuan Agricultural University (No. 20180805).
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Lin, Q., Fu, Q., Li, X. et al. Human β-Defensin 118 Attenuates Escherichia coli K88–Induced Inflammation and Intestinal Injury in Mice. Probiotics & Antimicro. Prot. 13, 586–597 (2021). https://doi.org/10.1007/s12602-020-09725-9
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DOI: https://doi.org/10.1007/s12602-020-09725-9