Inhibition of heparin synthesis by methotrexate in rats in vivo

Marcondes, Sisi; Baú, Elaine Cristina; Antunes, Edson; Dietrich, Carl P.; Nader, Helena B.; Nucci, Gilberto De

doi:10.1016/s0006-2952(02)01063-8

Cited by 2 publications

(2 citation statements)

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“…Role of mast cells and inflammatory bowel diseasechildren [183] , most likely through inhibition of mast cell and neutrophil degranulation [184] . It was surprising to learn that even immunomodulatory drug methotrexate, which showed promise in Crohn's disease therapy [185] was able to inhibit heparin synthesis in mast cells [186] , suggesting that the beneficial action of methotrexate on Crohn's disease might be due to the reduction of heparin secretion from mast cells. Nicotine, an addictive component of tobacco, had a dual effect on IBD.…”

Section: Relationship Between Therapies For Ibd and Mast Cellsmentioning

confidence: 99%

Key role of mast cells and their major secretory products in inflammatory bowel disease

He¹

2004

WJG

221

170

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Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNFα, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activationdegranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H 1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.He SH. Key role of mast cells and their major secretory products in inflammatory bowel disease.

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Section: Relationship Between Therapies For Ibd and Mast Cellsmentioning

confidence: 99%

Key role of mast cells and their major secretory products in inflammatory bowel disease

He¹

2004

WJG

221

170

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“…Indeed, mast cells have been demonstrated to regulate the intestinal epithelium permeability, to initiate and maintain the inflammatory response and are involved in tissue remodelling [7]. Interestingly, some of the conventional drug used for the management of IBD, such as 5-aminosalycilic acid, corticosteroids and even methotrexate, are considered to be effective, at least in part, by acting on mast cells [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

et al. 2018

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Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favourable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/mL, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H2O2-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

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Inhibition of heparin synthesis by methotrexate in rats in vivo

Cited by 2 publications

References 32 publications

Key role of mast cells and their major secretory products in inflammatory bowel disease

Key role of mast cells and their major secretory products in inflammatory bowel disease

Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

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