Imbalance of Controlled Death in Peripheral Blood Lymphocytes in Crohn’s Disease and Ulcerative Colitis

Dudzińska, Ewa; Szymona, Kinga; Gil-Kulik, Paulina; Chomik, Piotr; Świstowska, Małgorzata; Gryzińska, Magdalena; Kocki, Janusz

doi:10.3390/medicina55060231

Cited by 11 publications

(7 citation statements)

References 18 publications

(21 reference statements)

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“…Another important mechanism that plays a major role in the pathogenicity of UC is the apoptotic pathway, which is regulated by the balance between pro‐apoptotic proteins, such as BAX, BAD and BAK, and anti‐apoptotic proteins, such as BCL2, BCL‐XL and MCl‐1. An elevated BAX/BCL2 ratio can enhance the activity of caspase‐3, activating the apoptotic pathway 41 . BCL2, a prototype gene in the BCL family, exhibits anti‐apoptotic activity and is located in the outer leaflet of mitochondria.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

Bagalagel

Diri

Noor

et al. 2022

Basic Clin Pharma Tox

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Patients with ulcerative colitis (UC) experience diarrhoea, hematochezia and abdominal pain. UC is a well-known health challenge affecting 200-250 per 100 000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)-1α and miR-143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP-1α, B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), miR-143, NF-κB, tumour necrosis factor (TNF)-α and active caspase-3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin-eosin or immunostained with anti-TNF-α and anti-caspase-3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin-eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP-1α, BAX, NF-κB, TNF-α and active caspase-3, associated with BCL2 and miR-143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP-1α/miR-143, subsequently deactivating inflammatory and apoptotic pathways.K E Y W O R D S active caspase-3, B-cell lymphoma 2 (BCL2), BCL2 associated X (BAX), macrophage inflammatory protein (MIP)-1α, miR-143, nuclear factor (NF)κB, sphingosine kinase (SphK), tumour necrosis factor (TNF)-α

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Section: Discussionmentioning

confidence: 99%

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

Bagalagel

Diri

Noor

et al. 2022

Basic Clin Pharma Tox

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“…Additional emphasis was laid on genes involved in apoptosis and autophagy for their involvement in response to TNF-inhibitors, which affects the inflammatory immune response in IBD [ 27 ]. Among these genes, Fas and Fas-ligand (FasL) are particularly important in the downregulation of immunological processes [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of Biological Agents Used in Inflammatory Bowel Disease: A Systematic Review

et al. 2021

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Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn’s disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs with lower side effects quickly increased in the last decade. However, the presence of certain polymorphisms in the population may determine a different outcome in response to therapy, reflecting the heterogeneity of the efficacy in patients. Considering that several studies showed important correlations between genetic polymorphisms and response to biological treatments in IBD patients, this systematic review aims to summarize the pharmacogenetics of biologicals approved for IBD, thus highlighting a possible association between some polymorphisms and drug response. With this purpose, we reviewed PubMed papers published over the past 21 years (2000–2021), using as the search term “drug name and IBD or CD or UC and polymorphisms” to underline the role of pharmacogenetic tests in approaching the disease with a targeted therapy.

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“…Inflammatory bowel disease (IBD), which includes mainly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic and recurrent inflammatory condition of the gastrointestinal tract. 1,2 Protease genes constitute about 2% of the mammalian genome, and their gene products are enzymes considered essential for processes such as development, coagulation, immunity, inflammation and cell death. 3 The four categories of proteinases, cysteine, serine, aspartic, and metalloproteinases, are named and classified according to their essential catalytic component, usually an amino acid, in their active site.…”

Section: Introductionmentioning

confidence: 99%

Influence of the Treatment Used in Inflammatory Bowel Disease on the Protease Activities

Dudzińska¹,

Strachecka²,

Gil-Kulik³

et al. 2020

IJGM

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Introduction There is growing evidence that intestinal proteases have a role in the pathogenesis of gastrointestinal inflammatory diseases. Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), has an additional source of proteases represented by infiltrated and activated inflammatory cells. The aim of our study was to determine proteolytic system activity in patients with CD and UC. We limited the number of proteases tested by determining proteases active in acidic, neutral and alkaline pH. Materials and Methods The study included 40 patients with IBD – 20 CD patients and 20 UC patients. The control group consisted of 20 healthy subjects. Among the 20 CD patients, 17 were treated with aminosalicylates, 14 with azathioprine, and 4 with corticosteroids, while 8 patients were undergoing biological treatment. Among the 20 UC patients, 19 were treated with aminosalicylates, 8 with azathioprine, and 3 with corticosteroids. The total protein concentration was assayed by the Lowry method. The optimal pH was assayed in pH from 2.2 to 12.8, separated by 0.2 intervals. Proteolytic activities were determined against different substrates (gelatine, haemoglobin, ovalbumin, albumin, cytochrome C, and casein), and haemoglobin was the optimal substrate. Protease activities were determined according to Anson method. Determination of the activities of natural inhibitors of acidic, neutral and alkaline proteases is based on the Lee and Lin method. Results Decreases were observed in the activities of acid proteases (pH 5), alkaline proteases (pH 7), and neutral proteases (pH 7.6 and 8.6) in the groups of CD patients in remission in comparison with the active phase. In the group of patients with biologically treated CD patients, acid protease activity (pH 5.0) was lower than in CD patients not receiving biological treatment. Activities of neutral (pH 7.0) and alkaline (pH 7.6 and 8.6) proteases in the plasma of patients with UC in remission were lower in comparison to the active phase. Activities of acid (pH 5.0) and alkaline (8.6) protease inhibitors were higher in CD patients in the active phase in comparison to remission. In UC patients with exacerbation of the disease, the activity of alkaline (pH 8.6) protease inhibitors was increased compared to remission. Conclusion 1. Our research may suggest that the immunomodulatory treatment used in IBD, aimed at reducing the level of leukocytes and reduction of inflammation, may contribute to a reduction in protease activity. 2. The decrease of protease activities in patients with CD and UC in remission may be a marker suggesting the patients’ response to the treatment.

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Imbalance of Controlled Death in Peripheral Blood Lymphocytes in Crohn’s Disease and Ulcerative Colitis

Cited by 11 publications

References 18 publications

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

Pharmacogenetics of Biological Agents Used in Inflammatory Bowel Disease: A Systematic Review

Influence of the Treatment Used in Inflammatory Bowel Disease on the Protease Activities

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