Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2018; 24(6): 706-715
Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.706
Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats
Chun-Lan Xu, Yu Guo, Lei Qiao, Li Ma, Yi-Yi Cheng
Chun-Lan Xu, Yu Guo, Lei Qiao, Li Ma, Yi-Yi Cheng, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
Author contributions: Xu CL conceived and designed the experiments; Guo Y, Qiao L and Ma L performed the experiments; Cheng YY analyzed the data; Roman A contributed reagents/materials/analysis tools; Xu CL wrote the manuscript.
Supported by the National Natural Science Foundation of China, No. 31672435; the Graduate Starting Seed Fund of Northwestern Polytechnical University, No. Z2017236; and the National College Students Innovation, Experiment Program, No. 201610699266.
Institutional review board statement: The study was reviewed and approved by the Northwestern Polytechnical University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Northwestern Polytechnical University (IACUC protocol number: No.2016014).
Conflict-of-interest statement: No potential conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chun-Lan Xu, PhD, Associate Professor, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyixi Road, Xi’an 710072, Shaanxi Province, China. clxu@nwpu.edu.cn
Telephone: +86-29-88460543 Fax: +86-29-88460332
Received: December 1, 2017
Peer-review started: December 1, 2017
First decision: December 13, 2017
Revised: December 19, 2017
Accepted: December 27, 2017
Article in press: December 27, 2017
Published online: February 14, 2018
Processing time: 67 Days and 1.8 Hours
Abstract
AIM

To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

METHODS

Forty-eight rats were randomized into six groups: normal control group (Control), model control group (TNBS), ethanol treatment group (ETOH), and VIP treatment groups with different dosage (rVIPa1nmol, rVIPa2nmol, rVIPa4nmol). Diarrhea and bloody stool were observed. Colonic damage was evaluated histologically. The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), myeloperoxidase (MPO) and endotoxin in colonic tissue and serum were determined by enzyme-linked immunosorbent assay (ELISA). The expression of occludin, ZO-1, Toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65 (NF-κB p65), IκBα, and p-IκBα were detected by Western blot.

RESULTS

Administration with 2 nmol rVIPa prevented TNBS-induced necrosis, hyperemia, swelling, inflammation, etc., pathologic changes observed in the inner surface of colon in experimental rats. Moreover, rVIPa significantly decreased colonic TNF-α level (P < 0.001), MPO activity (P < 0.001) and serum endotoxin level (P < 0.01), and remarkably increased colonic IL-10 content (P < 0.001) in rats with TNBS-induced colitis. Furthermore, compared to the TNBS-induced colitis group, 2 nmol rVIPa treatment up-regulated the levels of occludin (P < 0.05) and ZO-1 (P < 0.05), NF-κB p65 (P < 0.01) and IκBα (P < 0.001), and down-regulated the levels of TLR4.

CONCLUSION

rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively protected the intestinal mucosal barrier function in rats. The mechanism may be related to TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders.

Keywords: Vasoactive intestinal peptide; Intestinal mucosal barrier; Tight junction; Toll-like receptors; Recombinant expression

Core tip: Vasoactive intestinal peptide (VIP) is a neuropeptide with potent anti-inflammatory activities. Recombinant VIP analogue (rVIPa with amino acid sequence “HSKAVFTKNYTRLRKQMAVKKYLNSILN”) with higher antimicrobial activity and stability than natural peptide was produced by an effective and low-cost production method. The current study first indicated that rVIPa could alleviated TNBS-induced colitis via TLR4/NF-κB-mediated signaling pathway. In summary, these results suggest a protective role and anti-inflammatory effect of rVIPa in inflammatory bowel disease and indicate that rVIPa has therapeutic potential for intestinal inflammatory disorders. The study contributes to identify and produce novel anti-inflammatory agents from human innate host defense mechanisms in the process of biological evolution.