CoChat
Sign Up
Cited by 130Inflammatory Bowel DiseaseGastrointestinal motility and disordersImmune Response and Inflammation

IL1β‐ and LPS‐induced serotonin secretion is increased in EC cells derived from Crohn’s disease

Open access
Kidd, M., Gustafsson, B. I., Drozdov, I., Modlin, I. M.·2009·Neurogastroenterology & Motility
DOI 10.1111/j.1365-2982.2008.01210.xPMC PMC4040949
Open this paper in CoChat — free account

Abstract

Abstract Gut mucosal enterochromaffin (EC) cells are regarded as key regulators of intestinal motility and fluid secretion via secretion of serotonin (5HT), are increased in numbers in mucosal inflammation and located in close proximity to immune cells. We examined whether interleukin (IL)1β and Escherichia coli lipopolysaccharide (LPS) induced EC cell 5HT release through Toll‐like/IL‐1 (TIL) receptor activation, nuclear factor kappa B (NFκB) and mitogen‐activated protein kinase (MAPK) phosphorylation and evaluated whether somatostatin could inhibit this phenomenon. Pure (>98%) human intestinal EC cells were isolated by fluorescent activated cell sorting from preparations of normal (n = 5) and Crohn’s colitis (n = 6) mucosa. 5HT release was measured (ELISA), and NFκB and ERK phosphorylation quantitated (ELISA) in response to IL1β and LPS. 5HT secretion was increased by both E. coli LPS (EC 50 = 5 ng mL−1) and IL1β (EC 50 = 0.05 pmol L−1) >2‐fold (P < 0.05) in Crohn’s EC cells compared with normal EC cells. Secretion was reversible by the TLR4 antagonist, E. coli K12 LPS (IC 50 = 12 ng mL−1) and the IL1β receptor antagonist (ILRA; IC 50 = 3.4 ng mL−1). IL1β caused significant (P < 0.05) NFκB and MAPK phosphorylation (40–55%). The somatostatin analogue, lanreotide inhibited IL1β‐stimulated secretion in Crohn’s (IC 50 = 0.61 nmol L−1) and normal EC cells (IC 50 = 1.8 nmol L−1). Interleukins (IL1β) and bacterial products (E. coli LPS) stimulated 5HT secretion from Crohn’s EC cells via TIL receptor activation (TLR4 and IL1β). Immune‐mediated alterations in EC cell secretion of 5HT may represent a component of the pathogenesis of abnormal bowel function in Crohn’s disease. Inhibition of EC cell‐mediated 5HT secretion may be an alternative therapeutic strategy in the amelioration of inflammatory bowel disease symptomatology.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1365-2982.2008.01210.x

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Bacterial LPS can increase 5-HT secretion via TLR4 activation in ECs isolated from Crohn's disease patients, but not from healthy subjects.

    “bacterial LPS can increase 5-HT secretion via TLR4 activation in ECs isolated from Crohn's disease patients, but not from healthy subjects (Kidd et al., 2009).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Kidd et al., 2009

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 68

  1. [1]Crowell MD Shetzline MA Moses PL Mawe GM Talley NJ Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function. Curr Opin Investig Drugs 2004 5 55 60 14983974
  2. [2]Thompson A Keelman M Thiesen A Clandinin M Ropeleski M Wild G Small bowel review: normal physiology part 2. Dig Dis Sci 2001 46 2588 607 11768248
  3. [3]Yang GB Lackner AA Proximity between 5-HT secreting enteroendocrine cells and lymphocytes in the gut mucosa of rhesus macaques (Macaca mulatta) is suggestive of a role for enterochromaffin cell 5-HT in mucosal immunity. J Neuroimmunol 2004 146 46 9 14698846
  4. [4]Wang H Steeds J Motomura Y CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection. Gut 2007 56 949 57 17303597 PMC1994360
  5. [5]Leon-Ponte M Ahern GP O'Connell PJ Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor. Blood 2007 109 3139 46 17158224 PMC1852236
  6. [6]Podolsky DK Inflammatory bowel disease. N Engl J Med 2002 347 417 29 12167685
  7. [7]Gershon M Review article: Serotonin receptors and transporters – roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 2004 20 Suppl. 7 3 14 15521849
  8. [9]Linden D Foley K McQuoid C Simpson J Sharkey K Mawe G Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis. Neurogastroenterol Motil 2005 17 565 74 16078946
  9. [10]Kyosola K Penttila O Salaspuro M Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. Scand J Gastroenterol 1977 12 363 7 867000
  10. [11]El-Salhy M Danielsson A Stenling R Grimelius L Colonic endocrine cells in inflammatory bowel disease. J Intern Med 1997 242 413 9 9408072
  11. [12]Belai A Boulos PB Robson T Burnstock G Neurochemical coding in the small intestine of patients with Crohn's disease. Gut 1997 40 767 74 9245931 PMC1027202
  12. [13]Rogler G Andus T Cytokines in inflammatory bowel disease. World J Surg 1998 22 382 9 9523521
  13. [14]Casini-Raggi V Kam L Chong YJ Fiocchi C Pizarro TT Cominelli F Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol 1995 154 2434 40 7868909
  14. [15]Minderhoud IM Oldenburg B Schipper ME Ter Linde JJ Samsom M Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission. Clin Gastroenterol Hepatol 2007 5 714 20 17481962
  15. [16]Yamamoto T Nakahigashi M Umegae S Kitagawa T Matsumoto K Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis 2005 11 580 8 15905706
  16. [18]Reubi JC Mazzucchelli L Laissue JA Intestinal vessels express a high density of somatostatin receptors in human inflammatory bowel disease. Gastroenterology 1994 106 951 9 8144000
  17. [19]Watanabe T Kubota Y Sawada T Muto T Distribution and quantification of somatostatin in inflammatory disease. Dis Colon Rectum 1992 35 488 94 1348980
  18. [20]Kidd M Modlin I Eick G Champaneria M Isolation, purification and functional characterization of the Mastomys EC cell. Am J Physiol 2006 291 G778 91 16455786
  19. [21]Modlin IM Kidd M Eick G Champaneria M The functional characterization of normal and neoplastic EC cells. J Clin Endocrinol Metab 2006 91 2340 8 16537680
  20. [22]Stevens C Walz G Singaram C Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci 1992 37 818 26 1587185
  21. [23]Gross V Andus T Leser HG Roth M Scholmerich J Inflammatory mediators in chronic inflammatory bowel diseases. Klin Wochenschr 1991 69 981 7 1798295
  22. [24]Fiocchi C Hilfiker ML Youngman KR Doerder NC Finke JH Interleukin 2 activity of human intestinal mucosa mononuclear cells. Decreased levels in inflammatory bowel disease. Gastroenterology 1984 86 734 42 6607860
  23. [25]Reinecker HC Steffen M Witthoeft T Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 1993 94 174 81 8403503 PMC1534387
  24. [26]Breese EJ Michie CA Nicholls SW Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology 1994 106 1455 66 8194690
  25. [27]Reimund JM Wittersheim C Dumont S Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease. Gut 1996 39 684 9 9026483 PMC1383392
  26. [28]Raab Y Gerdin B Ahlstedt S Hallgren R Neutrophil mucosal involvement is accompanied by enhanced local production of interleukin-8 in ulcerative colitis. Gut 1993 34 1203 6 8406154 PMC1375454
  27. [29]Cominelli F Pizarro TT Interleukin-1 and interleukin-1 receptor antagonist in inflammatory bowel disease. Aliment Pharmacol Ther 1996 10 Suppl. 2 49 53 discussion 54 8899101
  28. [30]Dionne S D'Agata ID Hiscott J Vanounou T Seidman EG Colonic explant production of IL-1 and its receptor antagonist is imbalanced in inflammatory bowel disease (IBD). Clin Exp Immunol 1998 112 435 42 9649212 PMC1904987
  29. [31]Mitsuyama K Sasaki E Toyonaga A Colonic mucosal interleukin-6 in inflammatory bowel disease. Digestion 1991 50 104 11 1804734
  30. [32]Waidmann M Bechtold O Frick JS Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice. Gastroenterology 2003 125 162 77 12851881
  31. [33]Kim SC Tonkonogy SL Albright CA Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 2005 128 891 906 15825073
  32. [34]Dunne A O'Neill LA The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003 2003 re3 12606705
  33. [35]Trinchieri G Sher A Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 2007 7 179 90 17318230
  34. [36]Kidd M Nadler B Mane SM GeneChip, geNorm and Gastrointestinal tumors: novel reference genes for real-time PCR. Physiol Genomics 2007 30 363 70 17456737
  35. [37]Kidd M Miu K Tang LH Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells. Gastroenterology 1997 113 1110 7 9322505
  36. [38]Grider JR Interleukin-1 beta selectively increases substance P release and augments the ascending phase of the peristaltic reflex. Neurogastroenterol Motil 2003 15 607 15 14651596
  37. [39]Kidd M Modlin I Gustafsson B Drozdov I Hauso O Pfragner R The luminal regulation of normal and neo-plastic EC cell serotonin release is mediated by bile salts, amines, tastants and olfactants. Am J Physiol 2008 295 G260 72 18556422
  38. [40]Sjolund K Sanden G Hakanson R Sundler F Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology 1983 85 1120 30 6194039
  39. [41]Barnett P Somatostatin and somatostatin receptor physiology. Endocrine 2003 20 255 64 12721505
  40. [42]Coughlin SR Moskowitz MA Antoniades HN Levine L Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor. Proc Natl Acad Sci USA 1981 78 7134 8 7031670 PMC349210
  41. [43]Buchheit KH Engel G Mutschler E Richardson B Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum. Evidence for two distinct release mechanisms. Naunyn Schmiedebergs Arch Pharmacol 1985 329 36 41 2582276
  42. [44]Siriwardena A Kellum JM Jr A 5-HT2 receptor mediates serotonin-induced electrolyte transport in rat left colon. J Surg Res 1993 55 323 9 8412118
  43. [45]Bobker DH Williams JT Serotonin-mediated inhibitory postsynaptic potential in guinea-pig prepositus hypoglossi and feedback inhibition by serotonin. J Physiol 1990 422 447 62 2141079 PMC1190142
  44. [46]Alvarado-Alvarez R Arechiga H Garcia U Serotonin activates a Ca(2+)-dependent K(+) current in identified peptidergic neurons from the crayfish. J Exp Biol 2000 203 715 23 10648213
  45. [47]Sidhu M Cooke HJ Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion. Am J Physiol 1995 269 G346 51 7573444
  46. [48]Cooke HJ Wang YZ Frieling T Wood JD Neural 5-hydroxytryptamine receptors regulate chloride secretion in guinea pig distal colon. Am J Physiol 1991 261 G833 40 1951703
  47. [49]Kidd M Eick GN Modlin IM Pfragner R Champaneria MC Murren J Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin. J Mol Endocrinol 2007 38 181 92 17242179
  48. [50]Kitaoka Y Munemasa Y Nakazawa T Ueno S NMDA-induced interleukin-1beta expression is mediated by nuclear factor-kappa B p65 in the retina. Brain Res 2007 1142 247 55 17320050
  49. [51]Lomax AE Linden DR Mawe GM Sharkey KA Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits. Auton Neurosci 2006 127 250 7 16616704
  50. [52]Caradonna L Amati L Magrone T Pellegrino NM Jirillo E Caccavo D Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res 2000 6 205 14 11052175
  51. [53]Pastor Rojo O Lopez San Roman A Albeniz Arbizu E de la Hera Martinez A Ripoll Sevillano E Albillos Martinez A Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease. Inflamm Bowel Dis 2007 13 269 77 17206721
  52. [54]Dionne S Laberge S Deslandres C Seidman EG Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease. Clin Exp Immunol 2003 133 108 14 12823284 PMC1808749
  53. [55]Cario E Podolsky DK Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000 68 7010 7 11083826 PMC97811
  54. [56]Franchimont D Vermeire S El Housni H Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut 2004 53 987 92 15194649 PMC1774122
  55. [57]Oostenbrug LE Drenth JP de Jong DJ Association between Toll-like receptor 4 and inflammatory bowel disease. Inflamm Bowel Dis 2005 11 567 75 15905704
  56. [58]Gazouli M Mantzaris G Kotsinas A Association between polymorphisms in the Toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population. World J Gastroenterol 2005 11 681 5 15655821 PMC4250738
  57. [59]Sandborn W Targan S Biologic therapy of inflammatory bowel disease. Gastroenterology 2002 122 1592 608 12016425
  58. [60]Ligumsky M Simon PL Karmeli F Rachmilewitz D Role of interleukin 1 in inflammatory bowel disease – enhanced production during active disease. Gut 1990 31 686 9 2379873 PMC1378497
  59. [61]Prinz C Neumayer N Mahr S Classen M Schepp W Functional impairment of rat enterochromaffin-like cells by interleukin 1 beta. Gastroenterology 1997 112 364 75 9024290
  60. [62]Doyle SL O'Neill LA Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol 2006 72 1102 13 16930560
  61. [64]Koch TR Carney JA Morris VA Go VL Somatostatin in the idiopathic inflammatory bowel diseases. Dis Colon Rectum 1988 31 198 203 2894935
  62. [66]Eliakim R Karmeli F Okon E Rachmilewitz D Octreo-tide effectively decreases mucosal damage in experimental colitis. Gut 1993 34 264 9 8381760 PMC1373982
  63. [67]Redmann A Rasch A Tourne H Mann K Petersenn S Characterization and transcriptional regulation of the human somatostatin receptor subtype 1 gene. Horm Metab Res 2007 39 359 65 17533578
  64. [68]Baumeister H Meyerhof W Gene regulation of somatostatin receptors in rats. J Physiol Paris 2000 94 167 77 11087993
  65. [69]Hofland LJ van Hagen PM Lamberts SW Functional role of somatostatin receptors in neuroendocrine and immune cells. Ann Med 1999 31 Suppl. 2 23 7 10574151
  66. [70]van Bergeijk JD Wilson JH Nielsen OH Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1). Eur J Gastroenterol Hepatol 2002 14 243 8 11953688
  67. [71]van der Hoek J van der Lelij AJ Feelders RA The somatostatin analogue SOM230, compared with octreo-tide, induces differential effects in several metabolic pathways in acromegalic patients. Clin Endocrinol (Oxf) 2005 63 176 84 16060911
  68. [72]Nilsson AH The gut as the largest endocrine organ in the body. Ann Oncol 2001 12 Suppl. 2 S63 8 11762354

Cited by

Sorted by citations

Authors
Kidd, M., Gustafsson, B. I., Drozdov, I., & Modlin, I. M.
Affiliations
Yale University (US)
Corresponding author
Kidd, M.
ORCID
Venue
Neurogastroenterology & Motility
Publisher
Wiley
Published
2009-03-11
Volume
21
Issue
4
Pages
439-450
ISSN
  • 1350-1925 (ISSN-L)
  • 1365-2982
DOI
10.1111/j.1365-2982.2008.01210.x
PMC
PMC4040949
OpenAlex
W2022783819
Cited by
130
References
3
Citations by year
2026: 3 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 13 · 2015: 5 · 2014: 2 · 2013: 10 · 2012: 10
FWCI
4.87
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Neurogastroenterology & Motility (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Yale University
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080871)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
enterochromaffin cells, serotonin release, Crohn's disease, IL-1β, lipopolysaccharide, TLR4, NF-κB, MAPK phosphorylation, somatostatin, lanreotide, intestinal inflammation, intestinal motility, inflammatory bowel disease pathogenesis, interleukin-1 receptor antagonist, TLR4 antagonist
MeSH terms
Crohn Disease, Enterochromaffin Cells, Enzyme-Linked Immunosorbent Assay, Escherichia coli, Flow Cytometry, Humans, Lipopolysaccharides, Phosphorylation, Serotonin, Signal Transduction, NF-kappa B, Reverse Transcriptase Polymerase Chain Reaction, Mitogen-Activated Protein Kinases, Toll-Like Receptors, Interleukin-1beta

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review