scholarly journals Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Weigang Shu ◽  
Zhi Pang ◽  
Chunjin Xu ◽  
Jian Lin ◽  
Gengfeng Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Iron Metabolism ◽  
Bowel Disease ◽  
Caspase 3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anemia Of Chronic Disease ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Inflammatory Bowel

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn’s disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

Vitamin D Decreases Hepcidin and Inflammatory Markers in Newly Diagnosed Inflammatory Bowel Disease Paediatric Patients: A Prospective Study

2019 ◽  
Vol 13 (10) ◽  
pp. 1287-1291 ◽  
Author(s):  
Hadar Moran-Lev ◽  
Tut Galai ◽  
Anat Yerushalmy-Feler ◽  
Yosef Weisman ◽  
Adi Anafy ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Bowel Disease ◽  
Signs And Symptoms ◽  
Newly Diagnosed ◽  
Hepcidin Expression ◽  
Hydroxyvitamin D ◽  
Paediatric Patients ◽  
Serum Hepcidin ◽  
Inflammatory Bowel

Abstract Background and Aims The role of hepcidin in inflammatory bowel disease [IBD] in children with anaemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD paediatric patients. Methods Eighty-five children were prospectively recruited in the Dana-Dwek Children’s Hospital [40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13.5 ± 3.4 years]. Blood samples for measurement of interleukin 6 [IL-6], C-reactive protein [CRP], hepcidin, iron parameters and 25-hydroxyvitamin D [25-(OH)-D] levels were obtained at baseline. Patients with mild-to-moderate signs and symptoms of IBD were treated with 4000 units of vitamin D daily for 2 weeks, after which the blood tests were repeated. Results Basal hepcidin, IL-6, CRP and platelet counts were significantly higher, and haemoglobin, serum iron and transferrin levels were significantly lower in the IBD children compared to controls [p < 0.001]. Eighteen patients completed 2 weeks of treatment with vitamin D. Following treatment, serum 25-(OH)-D concentrations increased by 40% [from 22.5 to 32.5 ng/mL], and serum hepcidin, CRP and ferritin levels decreased by 81%, 81% and 40% [from 33.9 to 6.7 ng/mL, from 23.9 to 4.7 mg/L, and from 27 to 16 ng/mL, respectively] [p ≤ 0.001]. Conclusion Serum hepcidin levels were significantly higher in IBD paediatric patients compared to controls. Following vitamin D treatment, serum hepcidin concentration decreased significantly. These findings suggest a potential role for vitamin D in treating anaemia in IBD children. ClinicalTrials.gov number NCT03145896

scholarly journals Results of Multiple Diagnostic Tests forMycobacterium avium subsp. paratuberculosis in Patients with Inflammatory Bowel Disease and in Controls

2000 ◽  
Vol 38 (12) ◽  
pp. 4373-4381 ◽  
Author(s):  
Michael T. Collins ◽  
Gorm Lisby ◽  
Claus Moser ◽  
Debra Chicks ◽  
Steen Christensen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Diagnostic Tests ◽  
Ex Vivo ◽  
The United States ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vitro Assay ◽  
Inflammatory Bowel ◽  
Ifn Γ

Mycobacterium avium subsp. paratuberculosishas been incriminated as a cause of Crohn's disease (CD); however, studies to date have been relatively small and generally only used a single diagnostic assay. The objective of the study was to reexamine the association of M. avium subsp.paratuberculosis and CD using multiple diagnostic tests. Five methods were used to detect M. avium subsp.paratuberculosis infections in 439 inflammatory bowel disease (IBD) patients and 324 control subjects in the United States and Denmark. Most assays were adaptations of diagnostic tests for this infection performed routinely on animals. PCR for IS900, a genetic element unique to M. avium subsp.paratuberculosis, was positive significantly more often on resected bowel and lymph node tissues from CD patients (19.0%) and ulcerative colitis (UC) patients (26.2%) than from controls (6.3%) (P < 0.05). Positive IS900 PCR results occurred more often in U.S. than in Danish IBD patients, 32.0 versus 13.3% (P = 0.025). The majority of Danish patients were bacillus Calmette-Guérin (Mycobacterium bovisBCG) vaccinated (CD, 77.5%; UC, 86.6%; controls, 83.0%) whereas none of the U.S. patients with IBD and only 2% of U.S. controls were vaccinated. Among Danish IBD patients, positive PCR findings were four times more common among subjects who were not BCG vaccinated (33.3%) than among BCG vaccinates (8.8%, P = 0.02). Culture of the same tissues tested by PCR using modified BACTEC 12B medium failed to grow M. avium subsp. paratuberculosisfrom patients or controls. U.S. CD patients had the highest serological evidence (enzyme-linked immunosorbent assay [ELISA] for serum antibodies) of M. avium subsp. paratuberculosisinfection (20.7% of patients positive) which was higher than for all UC patients studied (6.1%) or healthy controls (3.8%,P < 0.005). Among Danish patients alone, however, no significant differences in rates of ELISA-positive results among CD, UC, or control patients were found. For 181 study subjects, both IS900 PCR and ELISA were performed. Although 11 were ELISA positive and 36 were PCR positive, in no instance was a patient positive by both tests, suggesting that these states are mutually exclusive. Evaluation of cytokine-mediated immune responses of IBD patients was complicated by the influence of immunosuppressive therapy given most IBD patients. Gamma interferon (IFN-γ) release by peripheral blood leukocytes after M. avium purified protein derivative PPD antigen stimulation showed significantly lower responses in CD patients than in UC patients or controls in both U.S. (by ex vivo assay) and Danish (by in vitro assay) populations (P< 0.05). Interleukin-5 responses were not different among CD, UC, or control groups. Collectively, the PCR, ELISA, and IFN-γ tests forM. avium subsp. paratuberculosis together with the unexpected observation that BCG vaccination influenced M. avium subsp. paratuberculosis detection, lead us to conclude that M. avium subsp. paratuberculosis, or some similarly fastidious mycobacterial species, infects at least a subset of IBD patients. Whether the infection is primary (causal) or secondary, it may contribute to the etiopathogenesis of IBD.

P140 3D BIOENGINEERED TISSUE MODEL OF THE LARGE INTESTINE TO STUDY INFLAMMATORY BOWEL DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S34-S35
Author(s):  
Terrence Roh ◽  
Ying Chen ◽  
Harry Paul ◽  
Chengchen Guo ◽  
David Kaplan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Large Intestine ◽  
Intestinal Epithelium ◽  
Bowel Disease ◽  
Tissue Model ◽  
Inflammatory Bowel ◽  
Silk Scaffold ◽  
Subepithelial Layer ◽  
Migration Of Macrophages

Abstract An in vitro model of intestine epithelium with an immune compartment was bioengineered to mimic immunologic responses seen in inflammatory bowel disease [1]. While aspects of intestinal immunity can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelium comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy silk scaffolds. Confluent epithelial monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon γ resulted in morphology changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines associated with active inflammatory bowel disease, including CXCL10, IL-1β, IL-6, MCP-2, and MIP-1β. The macrophage layer enhanced epithelial and biochemical responses to inflammatory stimuli, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease. References: 6 Roh, T.T., et al., 3D bioengineered tissue model of the large intestine to study inflammatory bowel disease. Biomaterials, 2019: p. 119517. 7 In, J., et al., Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cellular and molecular gastroenterology and hepatology, 2015. 2(1): p. 48–62.e3. 8 Chen, Y., et al., In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS ONE, 2017. 12(11): p. e0187880. Colonoid and macrophage cultivation scheme in the 3D bilayer system. (A) Human monocytes were isolated from whole blood and human colonoids from large intestine biopsies were cultured according to established protocols [2]. (B) Cell suspensions of colonoids were seeded on the film surface on the inner silk scaffold and monocyte-derived macrophages were seeded throughout the porous outer silk scaffold using established protocols [3]. (C) The model is cultured for 3 weeks total with 2 weeks in High WNT media and 1 week in differentiation media based on established protocol. Colonoids are present in the model throughout the 3 week culture time. 2 sets of macrophages are added with the first set added after the first week of culture and the second set replacing the first set after the second week.

scholarly journals Food and Food Groups in Inflammatory Bowel Disease (IBD): The Design of the Groningen Anti-Inflammatory Diet (GrAID)

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1067
Author(s):  
Marjo J. E. Campmans-Kuijpers ◽  
Gerard Dijkstra
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Food Group ◽  
Dietary Guidelines ◽  
Current Evidence ◽  
Group Level ◽  
Food Groups ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Diet plays a pivotal role in the onset and course of inflammatory bowel disease (IBD). Patients are keen to know what to eat to reduce symptoms and flares, but dietary guidelines are lacking. To advice patients, an overview of the current evidence on food (group) level is needed. This narrative review studies the effects of food (groups) on the onset and course of IBD and if not available the effects in healthy subjects or animal and in vitro IBD models. Based on this evidence the Groningen anti-inflammatory diet (GrAID) was designed and compared on food (group) level to other existing IBD diets. Although on several foods conflicting results were found, this review provides patients a good overview. Based on this evidence, the GrAID consists of lean meat, eggs, fish, plain dairy (such as milk, yoghurt, kefir and hard cheeses), fruit, vegetables, legumes, wheat, coffee, tea and honey. Red meat, other dairy products and sugar should be limited. Canned and processed foods, alcohol and sweetened beverages should be avoided. This comprehensive review focuses on anti-inflammatory properties of foods providing IBD patients with the best evidence on which foods they should eat or avoid to reduce flares. This was used to design the GrAID.

scholarly journals DNA damage and apoptosis in blood neutrophils of inflammatory bowel disease patients and in Caco-2 cells in vitro exposed to betanin

2016 ◽  
Vol 70 ◽  
pp. 265-271 ◽  
Author(s):  
Małgorzata Zielińska-Przyjemska ◽  
Anna Olejnik ◽  
Agnieszka Dobrowolska-Zachwieja ◽  
Michał Łuczak ◽  
Wanda Baer-Dubowska
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dna Damage ◽  
Bowel Disease ◽  
Blood Neutrophils ◽  
Inflammatory Bowel

scholarly journals Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

2020 ◽  
Vol 295 (13) ◽  
pp. 4237-4251 ◽  
Author(s):  
Jie Zhang ◽  
Min Xu ◽  
Weihua Zhou ◽  
Dejian Li ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cell ◽  
Bowel Disease ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
P53 Expression ◽  
Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

Sign in / Sign up

Export Citation Format

Share Document