Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.706
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
Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) Prolonged inflammation of the intestinal tract affects the patients’ quality of life and increases the risk of colorectal cancer development. Endogenous antimicrobial and immunoregulatory peptides represent an emerging category of therapeutic agents, are gaining considerable interest in the scientific community. VIP is a neuropeptide with potent anti-inflammatory activities. Recombinant expressed VIP analogue with higher antimicrobial activity and stability than natural peptide was produced by an effective and low-cost production method. The results indicated that rVIPa alleviated TNBS-induced colitis via TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders. The study contributes to advancement in novel treatment design.
At present, a proportion of patients with Crohn’s disease could not obtain high efficacy of the available medical therapies. Therefore, it is urgent to develop new anti-inflammatory agents with high efficacy, safety and low cost. The natural biological peptides and their analogues will provide important and significant resources for the development of molecules that can block inflammatory pathways.
rVIPa with high antimicrobial activity and stability was produced by an effective and low-cost biotechnology. The current study was conducted to investigate the modulatory effect of rVIPa on colon in rats with TNBS-induced colitis. The study contributes to the development of a kind of new and novel therapeutic agent from endogenous bioactive peptides for IBD.
The current study investigated the anti-inflammatory activity, and the possible mechanism of rVIPa through establishing acute colitis model in rats administrated of TNBS intrarectally. In addition to the body weight change, histological assessment, MPO and endotoxin analyzed by ELISA, and tight junction proteins levels analyzed by Western Blot, TLR4/NF-κB-mediated signaling pathway were also investigated.
The current study first find that VIP analogue produced by recombinant expression significantly ameliorates the colon injury and inflammation caused by TNBS in rats, and exhibits a protective effect on colitis. Moreover, administration with rVIPa inhibited proinflammatory cytokines, up-regulated tight junction proteins expression, and promotion of anti-inflammatory cytokines via TLRs/NF-κB signaling pathway.
rVIPa alleviated TNBS-induced inflammation and effectively protected the intestinal mucosal barrier function in rats, which may be related to TLR4/NF-κB-mediated signaling pathway. These results suggested that rVIPa could be explored to a new alternative therapy for intestinal inflammatory disorders.
By rational design and molecular modification, the antimicrobial and anti-inflammatory activity, and stability for endogenous bioactive peptides could be further improved. This study provides a simple, low-cost strategy for identifying and producing a novel anti-inflammatory agent from human innate host defense mechanisms in the process of biological evolution.