Where are we heading to in pharmacological IBD therapy?

Rogler, Gerhard

doi:10.1016/j.phrs.2015.07.005

Cited by 39 publications

(23 citation statements)

References 113 publications

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“…Reparixin, a noncompetitive inhibitor of the CXCL8 receptor (CXCR1 and CXCR2), were shown to prevent polymorphonuclear leukocyte recruitment and associated tissue damage in ischemia-reperfusion and organ transplantation and went to a Phase II clinical trial (NCT01220856) [159]. MDX-1100, a human anti-CXCL10 mAb in a placebo-controlled clinical trial in patients having moderate to severe UC, did not show a significant and positive clinical response [160]. Many of the chemokine receptor antagonist-based therapy also had been tried on cancer, transplantation, and nongut-associated autoimmune diseases with very low success.…”

Section: Chemokine-chemokine Receptors Used As Therapeutics To Contromentioning

confidence: 99%

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance

Kulkarni

Pathak

Lal

2016

Journal of Leukocyte Biology

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The intestinal epithelial lining is a very dynamic interface, where multiple interactions occur with the external world. The intestinal epithelial barrier is continuously exposed to a huge load of commensal microorganisms, food-borne antigens, as well as invading enteropathogens. Intestinal epithelial cells (IECs) and underlying immune cells are the main players in maintaining the delicate balance between gut tolerance and inflammation. IECs deferentially express the variety of chemokines and chemokine receptors, and these receptor-ligand interactions not only mediate the infiltration and activation of immune cells but also switch on the survival cascades in IECs. In this review, we discussed how chemokine-chemokine receptor-induced interactions play a central role to coordinate the interplay between IECs and gut immune cells to maintain homeostasis or elicit gut inflammation. Furthermore, we discussed how chemokines and chemokine receptors were used as a target for developing new drugs and therapies to control gut inflammation and autoimmunity.

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Section: Chemokine-chemokine Receptors Used As Therapeutics To Contromentioning

confidence: 99%

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance

Kulkarni

Pathak

Lal

2016

Journal of Leukocyte Biology

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“…In our experimental procedure, sulfasalazine did not prevent the increase of IL-6 induced by AOM/DSS-treatment; in contrast, shikonin did significantly inhibit this cytokine. Growing evidence supports a critical role for IL-6 signaling during CRC development, and so therapeutics that target this cytokine are viewed as promising options for the treatment of IBD [13,26].…”

Section: Discussionmentioning

confidence: 99%

Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells

et al. 2018

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Shikonin is the main active principle in the root of , widely used in traditional Chinese medicine for its anti-inflammatory and wound healing properties. Recent research highlights shikonin's antitumor properties and capacity to prevent acute ulcerative colitis. The aim of the present study was to evaluate the ability of shikonin to prevent,, the early phases of colorectal cancer development, with special focus on its cytotoxic mechanism . We employed the azoxymethane/dextran sulfate sodium model of colitis in Balb/C mice. Body weight and drinking were monitored throughout the experiment, and length of colon and lesions of the colon were recorded on termination of the experiment in all of the experimental groups. Colons underwent histological evaluation and biochemical analyses [myeloperoxidase activity assay, measurement of interleukin-6, evaluation of proinflammatory enzymes (cyclooxygenase-2 and inducible nitric oxide synthase), and nuclear factor-B activation by Western blot]. Caco-2 cells were used to evaluate, , the effect of shikonin on proliferation, cytotoxicity, cell cycle, and apoptosis. Our results reveal that shikonin significantly protected the intestinal tissue of our animals by preventing the shortening of the colorectum and ulcer formation in a dose-dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the production of interleukin-6 and activation of nuclear factor-B. It induced Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive agent in the azoxymethane/dextran sulfate sodium model through inhibition of the proinflammatory milieu generated during the disease, an important risk factor in cancer development.

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“…While only surgery is curative, immune-suppressive drugs have proved to be the most effective pharmacological treatment of the disease. In particular anti-tumour necrosis factor (TNF) therapy has shown to be crucial in treatment of severe cases [6,7].…”

Section: Introductionmentioning

confidence: 99%

Mucosal gene transcription of ulcerative colitis in endoscopic remission

Arkteg

Goll

Gundersen

et al. 2020

Scandinavian Journal of Gastroenterology

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Aim/Objective: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. In UC, a wide range of criteria are used for disease remission, with few studies investigating the differences between disease remission and normal control groups. This paper compares known inflammatory and healing mediators in the mucosa of UC in clinical remission and normal controls, in order to better describe the remission state. Method: Mucosal biopsies from 72 study participants (48 UC and 24 normal controls) were included from the Advanced Study of Inflammatory Bowel Disease (ASIB Study), Arctic University of Norway, Norway. Clinical remission was defined as Mayo clinical score 2, with endoscopic subscores of 1. Targeted gene transcription analyses were performed using hydrolysis probes and SYBR-green. Results: Among the mucosal transcripts examined, 10 genes were regulated in remission versus normal controls, 8 upregulated pro-inflammatory transcripts (IL1B, IL33, TNF, TRAF1, CLDN2, STAT1, STAT3 and IL13Ra2) and 2 downregulated (pro-inflammatory TBX21 and anti-inflammatory TGFB1). In total, 14 transcripts were regulated between the investigated groups. Several master transcription factors for Tcell development were upregulated in patients with Mayo endoscopic score of 1 in comparison to 0. Conclusions: The mucosa of UC in clinical and endoscopic remission differs from normal mucosa, suggesting a remaining dysregulation of inflammatory and wound healing mechanisms.

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Where are we heading to in pharmacological IBD therapy?

Cited by 39 publications

References 113 publications

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance

Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells

Mucosal gene transcription of ulcerative colitis in endoscopic remission

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