scholarly journals The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis

2020 ◽  
Vol 319 (6) ◽  
pp. G761-G768
Author(s):  
Jonas Woll Jørandli ◽  
Silje Thorsvik ◽  
Helene Kolstad Skovdahl ◽  
Benedikt Kornfeld ◽  
Siri Sæterstad ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Intestinal Epithelium ◽  
Serotonin Reuptake ◽  
Tryptophan Hydroxylase ◽  
Intestinal Inflammation ◽  
Serotonin Synthesis ◽  
Crohn’S Colitis ◽  
Tnf Α ◽  
Serotonin Reuptake Transporter

The serotonin reuptake transporter is potently reduced in inflamed areas of Crohn’s ileitis, Crohn’s colitis, and ulcerative colitis. The changes are localized to the intestinal epithelium and can be induced by TNF-α. The serotonin synthesis through tryptophan hydroxylase 1 is unchanged. This regulation is suggested as a mechanism underlying the increased extracellular serotonin levels associated with intestinal inflammation.

scholarly journals Two for One: Coexisting Ulcerative Colitis and Crohn’s Disease

2002 ◽  
Vol 16 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Grant I Chen ◽  
Fred Saibil ◽  
Izabella Morava-Protzner
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ulcerative Proctitis ◽  
Crohn’S Colitis ◽  
Crohn's Colitis ◽  
First Case ◽  
History Of

Three cases of coexisting ulcerative colitis and Crohn’s disease are presented. In the first case, the patient had a long-standing history of ulcerative proctitis before developing Crohn’s colitis. In the two remaining cases, the patients presented initially with Crohn’s disease of the ileum and, subsequent to resection, developed ulcerative colitis. Well-documented cases of patients diagnosed with both ulcerative colitis and Crohn’s disease are rare. The literature on such cases is reviewed, and the controversy over whether ulcerative colitis and Crohn’s disease are two distinct diseases is explored.

Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Physiological Basis ◽  
Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice

2009 ◽  
Vol 296 (3) ◽  
pp. G685-G695 ◽  
Author(s):  
Stephan C. Bischoff ◽  
Reiner Mailer ◽  
Oliver Pabst ◽  
Gisela Weier ◽  
Wanda Sedlik ◽  
...  
Keyword(s):  
Serotonin Reuptake ◽  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Colonic Motility ◽  
Trinitrobenzene Sulfonic Acid ◽  
Targeted Deletion ◽  
Immune Mediated ◽  
Serotonin Reuptake Transporter

Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.

scholarly journals Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Pathological Section ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Indigo Naturalis ◽  
Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

scholarly journals Comorbid Inflammatory Diseases of Digestive System and Eye

2021 ◽  
Vol 18 (1) ◽  
pp. 20-29
Author(s):  
S. A. Bulgakov ◽  
G. M. Chernakova ◽  
E. A. Kleshcheva ◽  
S. V. Simonova
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Ophthalmological Examination ◽  
Extraintestinal Manifestations ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.

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