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Human β-Defensin 118 Attenuates Escherichia coli K88–Induced Inflammation and Intestinal Injury in Mice

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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.

Funding

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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Authors

Contributions

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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Correspondence to Jun He.

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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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Fig S1

Analysis of the recombinant DEFB118 protein by SDS-PAGE. Lane 1, recombinant protein DEFB118 (with IPTG induction, protein molecular weight: 48.7 kDa); Lane 2, recombinant protein DEFB118 (without IPTG induction); M, protein marker. (PNG 686 kb)

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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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