title: Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.
authors.affiliation: 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.
authors.forename: Arseima Y
authors.initials: AY
authors.lastname: Del Valle-Pinero
authors.affiliation: 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.
authors.forename: LeeAnne B
authors.initials: LB
authors.lastname: Sherwin
authors.affiliation: 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.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Anderson
authors.affiliation: 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.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Caudle
authors.affiliation: 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.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003092:Colitis / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006930:Hyperalgesia / Q000097:blood / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D043183:Irritable Bowel Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold; D009195:Peroxidase / Q000097:blood; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D014660:Vasoactive Intestinal Peptide / Q000097:blood* / Q000235:genetics; D059265:Visceral Pain / Q000097:blood / Q000503:physiopathology; D015431:Weight Loss; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase
keywords: Gene expression; Irritable bowel syndrome; PCR arrays; Trinitrobenzene sulfonic acid; Vasoactive intestinal peptide