Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 155-163
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.155
Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis
Arseima Y Del Valle-Pinero, LeeAnne B Sherwin, Ethan M Anderson, Robert M Caudle, Wendy A Henderson
Arseima Y Del Valle-Pinero, LeeAnne B Sherwin, Wendy A Henderson, Digestive Disorders Unit, Biobehavioral Branch, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States
Arseima Y Del Valle-Pinero, Ethan M Anderson, Robert M Caudle, Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, United States
Robert M Caudle, Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, FL 32610, United States
Author contributions: Del Valle-Pinero AY, Anderson EM, and Caudle RM participated in the animal experiments; Del Valle-Pinero AY, Caudle RM and Henderson WA participated in the conception, design; Del Valle-Pinero AY, Sherwin LB and Henderson WA participated in the human components of the research; all authors contributed to data acquisition, interpretation and analysis of the data in addition to the drafts and revisions of the manuscript; all authors have approved the final version of the manuscript to be published.
Supported by National Institutes of Health grant, No. NS045614 and the Ruth L. Kirschstein National Research Service Award, No. 1F31 DK083165-01A1 from the National Institute of Diabetes and Digestive and Kidney Diseases; Division of Intramural Research, National Institute of Nursing Research, No. 1ZIANR000018-01-05 to Henderson WA and Intramural Training Award to Del Valle-Pinero AY and Sherwin LB
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: Dr. Wendy A Henderson, PhD, Chief, Digestive Disorders Unit, Biobehavioral Branch, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States. hendersw@mail.nih.gov
Telephone: +1-301-4519534 Fax: +1-301-4801413
Received: September 9, 2014
Peer-review started: September 10, 2014
First decision: October 14, 2014
Revised: October 29, 2014
Accepted: November 18, 2014
Article in press: December 16, 2014
Published online: January 7, 2015
Processing time: 120 Days and 5.4 Hours
Abstract

AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.

METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.

RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193).

CONCLUSION: Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.

Keywords: Irritable bowel syndrome; Vasoactive intestinal peptide; Trinitrobenzene sulfonic acid; Gene expression; PCR arrays

Core tip: The present study reports evidence of altered vasoactive intestinal peptide (VIP) in both humans with irritable bowel syndrome (IBS) and a rat model with induced colitis by trinitrobenzene sulfonic acid. Together these observations provide additional evidence of the role of VIP, and the potential therapeutic application in patients with IBS. The results provide a basis for future studies to elucidate the understanding of the expression, physiology, and pharmacological properties of VIP.