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