Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease

Söderholm, Johan D.; Olaison, Gunnar; Peterson, KH; Franzén, LE; Lindmark, Tuulikki; Wirén, Mikael; Tagesson, Christer; Sjödahl, Rune

doi:10.1136/gut.50.3.307

Cited by 241 publications

(188 citation statements)

References 52 publications

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“…39,40) Bacterial translocation plays a major pathogenic role in the development of enteropathy. 43,44) Secondly, it was found that OGT prevented serum NOx elevation induced by indomethacin (Fig. 6), and in a previous study, it was found that OGT strongly inhibits inducible nitric oxide synthase (iNOS) induction in lipopolysaccharide-stimulated macrophages.…”

Section: Fig 10 Localization Of Cox-2 Expressing Cellsmentioning

confidence: 78%

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Miura

Fukutake

Yamamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Prostaglandin E2 (PGE2) is a key regulator of gastrointestinal, immunological, and mucosal homeostasis. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the prostaglandin-producing enzyme cyclooxygenases (COXs), and can induce serious complications, such as gastrointestinal damage, with long-term treatment. Orengedokuto (OGT), a Japanese traditional herbal medicine (Kampo medicine), is effective in various animal models of enteropathy. In the present study we examined whether OGT prevents enteropathy induced by NSAIDs in mice. Ulceration in the small intestine was induced with 2 subcutaneous injections of indomethacin (20 mg/kg body weight). Orally administered OGT prevented or reduced lethality, intestinal lesions, bleeding, increased serum nitrate/nitrite levels, and reduction of mucosal PGE2 induced by indomethacin. These beneficial effects of OGT were accompanied by increased production of PGE2 and interleukin 10 by isolated lamina propria mononuclear cells; COX-2 in these cells may be a major source of PGE2 in normal intestines. These findings suggest that OGT could be an effective therapeutic agent for the treatment of inflammatory bowel disease and adverse reactions to NSAIDs.Key words nonsteroidal anti-inflammatory drug; interleukin 10; herbal medicine; inflammatory bowel disease; prostaglandin E2

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Section: Fig 10 Localization Of Cox-2 Expressing Cellsmentioning

confidence: 78%

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Miura

Fukutake

Yamamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Barrier maintenance requires an intricate balance between AJC and cytoskeletal rearrangements that facilitate continual IEC turnover and transepithelial transport, both energy-dependent processes. Reduced ATP levels have been observed in inflamed IBD biopsies (20), and noninflamed tissues from Crohn disease (CD) patients are more sensitive to uncoupling of oxidative phosphorylation (21). Dietary Cr supplementation has been shown to confer protection in multiple disease models that display bioenergetic dysregulation (22,23).…”

Section: Loss Of Hif Signaling Results In Altered Ck/pcr Circuit In Imentioning

confidence: 99%

Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis

Glover

Bowers²,

Saeedi³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

121

134

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Mucosal surfaces of the lower gastrointestinal tract are subject to frequent, pronounced fluctuations in oxygen tension, particularly during inflammation. Adaptive responses to hypoxia are orchestrated largely by the hypoxia-inducible transcription factors (HIFs). As HIF-1α and HIF-2α are coexpressed in mucosal epithelia that constitute the barrier between the lumen and the underlying immune milieu, we sought to define the discrete contribution of HIF-1 and HIF-2 transactivation pathways to intestinal epithelial cell homeostasis. The present study identifies creatine kinases (CKs), key metabolic enzymes for rapid ATP generation via the phosphocreatine-creatine kinase (PCr/CK) system, as a unique gene family that is coordinately regulated by HIF. Cytosolic CKs are expressed in a HIF-2-dependent manner in vitro and localize to apical intestinal epithelial cell adherens junctions, where they are critical for junction assembly and epithelial integrity. Supplementation with dietary creatine markedly ameliorated both disease severity and inflammatory responses in colitis models. Further, enzymes of the PCr/CK metabolic shuttle demonstrate dysregulated mucosal expression in a subset of ulcerative colitis and Crohn disease patients. These findings establish a role for HIF-regulated CK in epithelial homeostasis and reveal a fundamental link between cellular bioenergetics and mucosal barrier.epithelial junctions | energy metabolism | actomyosin | IBD

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“…In patients with Crohn's disease the gross macroscopic inflammation tends to occur in segments, whereas the observed pathophysiological features are found to be distributed throughout the gut. Examples of these are the distribution of T-lymphocyte aggregates (44), the status of tight junctions (49,62) and epithelial permeability (63,64), the neurotransmitter coding of enteric neurons (58), the expression of substance P and its receptor (27,42,54), the expression of tumor necrosis factor alpha by mast cells and of its inducer (lipopolysaccharide-induced tumor necrosis alpha factor) by macrophages (36,67), the composition of the intestinal flora (28), and the reduction in antimicrobial activity in the colon (47). An interesting feature of the present study was that there was no statistically significant association between the distribution of positive Mycobacterium avium subsp.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

Scanu¹,

et al. 2007

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Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P ‫؍‬ 0.0003 for irritable bowel syndrome patients versus healthy controls and P ‫؍‬ 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P ‫؍‬ 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of handmade cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.

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Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease

Cited by 241 publications

References 52 publications

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

An Herbal Medicine Orengedokuto Prevents Indomethacin-Induced Enteropathy

Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

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