lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

β-Defensin 129 Attenuates Bacterial Endotoxin-Induced Inflammation and Intestinal Epithelial Cell Apoptosis

34 Pages Posted: 26 Apr 2019

See all articles by Kunhong Xie

Kunhong Xie

Sichuan Agricultural University - Institute of Animal Nutrition

Hongmei Xie

Shandong Vocational Animal Science and Veterinary College

Guoqi Su

Sichuan Agricultural University - Institute of Animal Nutrition

Daiwen Chen

Sichuan Agricultural University - Institute of Animal Nutrition

Bing Yu

Sichuan Agricultural University - Institute of Animal Nutrition

Xiangbing Mao

Sichuan Agricultural University - Institute of Animal Nutrition

Zhiqing Huang

Sichuan Agricultural University - Institute of Animal Nutrition

Jie Yu

Sichuan Agricultural University - Institute of Animal Nutrition

Junqiu Luo

Sichuan Agricultural University - Institute of Animal Nutrition

Ping Zheng

Sichuan Agricultural University - Institute of Animal Nutrition

Yuheng Luo

Sichuan Agricultural University - Institute of Animal Nutrition

Jun He

Sichuan Agricultural University - Institute of Animal Nutrition

More...

Abstract

Background: Defensins have attracted considerable research interest worldwide because of their potential to serve as a substitute for antibiotics. In this study, we characterized a novel porcine β-defensin (pBD129) and explored its role in alleviating bacterial endotoxin-induced inflammation and intestinal epithelium atrophy.

Methods: The pBD129 gene was cloned and expressed in Escherichia coli. A recombinant pBD129 protein was purified. To explore its role in alleviating the endotoxin-induced inflammation, mice with or without lipopolysaccharide (LPS) challenge were treated by the pBD129 at different doses.

Results: The recombinant pBD129 showed significant antimicrobial activities against the E. coli and Streptococcus with a minimal inhibitory concentration (MICs) of 32 μg/mL. Hemolytic assays showed that the pBD129 had no detrimental impact on cell viabilities. Interestingly, we found that pBD129 attenuated LPS-induced inflammatory responses by decreasing serum concentrations of inflammatory cytokines such as the IL-1β, IL-6, and TNF-α (P<0.05). Moreover, pBD129 elevated the intestinal villus height (P<0.05) and enhanced the expression and localization of the major tight junction-associated protein ZO-1 in LPS-challenged mice. Additionally, pDB129 at a high dose significantly decreased serum diamine oxidase (DAO) concentration (P<0.05) and reduced intestinal epithelium cell apoptosis (P<0.05) in LPS-challenged mice. Importantly, pBD129 elevated the expression level of Bcl-2-associated death promoter (Bcl-2), but down-regulated the expression levels of apoptosis-related genes such as the B-cell lymphoma-2-associated X protein (Bax), BH3-interacting domain death agonist (Bid), cysteinyl aspartate-specific proteinase-3 (Caspase-3), and caspase-9 in the intestinal mucosa (P<0.05).

Conclusions: These results suggested a novel function of the mammalian defensins, and the anti-bacterial and anti-inflammatory properties of pBD129 may allow it a potential substitute for conventionally used antibiotics or drugs.   

Funding: This study was supported by the key Research and Development program of Sichuan Province (2018NZDZX0005) and the Youth Innovation teams of animal Feed Biotechnology of Sichuan Province (2016TD0028)

Declaration of Interest: The authors confirm that this article content has no conflict of interest.

Ethical Approval: The animal trial was approved by the Animal Welfare Committee of Sichuan Agricultural University (No. 20180718).

Keywords: Endotoxemia; Inflammation; Porcine β-defensin 129; Intestinal epithelium; Apoptosis

Suggested Citation

Xie, Kunhong and Xie, Hongmei and Su, Guoqi and Chen, Daiwen and Yu, Bing and Mao, Xiangbing and Huang, Zhiqing and Yu, Jie and Luo, Junqiu and Zheng, Ping and Luo, Yuheng and He, Jun, β-Defensin 129 Attenuates Bacterial Endotoxin-Induced Inflammation and Intestinal Epithelial Cell Apoptosis (04/23/2019 04:16:47). Available at SSRN: https://ssrn.com/abstract=3377507

Kunhong Xie

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Hongmei Xie

Shandong Vocational Animal Science and Veterinary College

China

Guoqi Su

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Daiwen Chen

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Bing Yu

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Xiangbing Mao

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Zhiqing Huang

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Jie Yu

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Junqiu Luo

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Ping Zheng

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Yuheng Luo

Sichuan Agricultural University - Institute of Animal Nutrition

Chengdu, 611130
China

Jun He (Contact Author)

Sichuan Agricultural University - Institute of Animal Nutrition ( email )

Chengdu, 611130
China

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
31
Downloads
2