Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats

Abstract

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

Vasoactive Intestinal Polypeptide (VIP) in the Intestinal Mucosal Nerve Fibers in Dogs with Inflammatory Bowel Disease

“…Since VIP shows neuroprotective properties [ 15 , 16 , 17 , 18 , 19 , 20 ], controls the immune reactions [ 41 ] and plays a key role during inflammatory processes [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], the possibility of the use of VIP analogs as drugs during intestinal inflammations has been tested in recent years. The results showed that VIP analogs ameliorated changes in the colon after experimentally induced colitis in rats and reduced necrosis, hyperemia and swelling [ 24 ].…”

Rottlerin ameliorates DSS-induced colitis by improving intestinal barrier function via activation of the Epac-2/Rap-1 signaling pathway

“…Intestinal permeability in mice was detected, the datas suggested that serum glucan binding levels in the rottlerin team were below those in the only DSS-treated mice, but similar to the WT mice (Figure 2E). Bacteria extracted from mln 10 and liver tissue are cultured by aseptic technology. In the rottlerin group, the probability of bacterial transfer to liver and MLN was below the DSS-treated group, but similar to the WT mice (Figure 2F-G).…”

“…Several bacterial pathogens can alter TJs by altering the distribution of occludin and ZO-1. The abnormal expression of TJ proteins in the epithelial cell monolayer may disrupt the structure and function of TJs, thereby destroying the completeness of barrier [10] . Inflammation is considered to be the basic mechanism of the pathophysiology of intestinal damage [11] .…”

Investigating Gut Permeability in Animal Models of Disease

“…Dietary and microbiota changes can protect the intestinal barrier function, which is the case for glutamine (Li et al, 1994), bacteria-derived lactic acid (Ren et al, 2018) and butyrate (Kelly et al, 2015). Other interventions disrupt the gut barrier, as in the case of DSS (Poritz et al, 2007), TNBS (Bregeon et al, 2016; Xu et al, 2018) or heavy metal supplementation (Zhai et al, 2016), low protein (Eyzaguirre-Velasquez et al, 2017) or high fat diet (Hamilton et al, 2015), infection (Guttman et al, 2006; Goossens et al, 2018) or CLP (Parida et al, 2015). These models can be considered to have good construct validity for organic diseases (i.e., those where morphological and/or biochemical features are altered) where barrier function is compromised.…”

“…These models can be considered to have good construct validity for organic diseases (i.e., those where morphological and/or biochemical features are altered) where barrier function is compromised. For example, DSS or TNBS supplementation in rodents and IL-10 knockout mice are well known models of colitis (Shi et al, 2014; Li et al, 2018; Xu et al, 2018), which is achieved through different mechanisms: DSS induces epithelial injury with exposure of the lamina propria and submucosa to luminal antigens, resulting in inflammation which ultimately alters the gut barrier; TNBS acts as a hapten and also induces inflammation but through Th1-mediated immune responses, which has been shown both in murine (Low et al, 2013) and swine models (Bregeon et al, 2016). IL-10 knockout mice spontaneously develop bowel inflammation, which is associated to colon dysbiosis (Shi et al, 2014).…”