scholarly journals E.coli JM83 Damages Mucosal Barrier Inducing Hirschsprung-Associated Enterocolitis via Activated TLR4 / NF-κB / P-p38 Signaling

2021 ◽  
Author(s):  
Zebing Zheng ◽  
Mingjuan Gao ◽  
Chengyan Tang ◽  
Lu Huang ◽  
Yuan Gong ◽  
...  
Keyword(s):  
Mucosal Damage ◽  
Mucosal Barrier ◽  
Endothelin Receptor ◽  
Oral Gavage ◽  
E Coli ◽  
Treatment And Prevention ◽  
Tnf Α ◽  
Study Results ◽  
Actin Protein

Abstract Purpose Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and unbalance of intestinal microbiota. Recent studies have shown that the TLR4/NF-κB/p-p38 signaling in the intestine is of great importance to intestinal mucosal integrity. This study aimed to investigate the role of TLR4/NF-κB/p-p38 signaling in the pathogenesis of HAEC in Escherichia coli (E. coli) JM83 infected Endothelin receptor B (Ednrb)−/− mice. Methods Ednrb −/− mice were administered with E. coli JM83 by oral gavage to establish the HAEC model, mice were randomly divided into WT group, Ednrb−/− group and Ednrb−/−+ E. coli JM83 group. The role of TLR4/NF-κB/p-p38 signaling was evaluated by vivo study. Results The activation of the TLR4/NF-κB/p-p38 signaling induced by E. coli JM83 caused HAEC in Ednrb−/− mice, which was evidenced by a significantly increased expression of TNF-α, TGF-β and IL-10, decreased density of F-actin protein. While TLR4 knockdown improved the degree of enterocolitis and attenuated the expression of IL-10, TNF-α, TGF-β and increased the density of F-actin protein in Ednrb−/− mice after E. coli infection. Conclusions These results indicate that E. coli JM83 activates TLR4/NF-κB/p-p38 signaling to promote the development of HAEC. However, inhibition of this signaling may be benefit to the treatment and prevention of HAEC.

scholarly journals Role of interleukin-1 and tumour necrosis factor in leukocyte recruitment to acute dermal inflammation

1992 ◽  
Vol 1 (5) ◽  
pp. 347-353 ◽  
Author(s):  
Andrew C. Issekutz ◽  
Nancy Lopes ◽  
Thomas B. Issekutz
Keyword(s):  
Monoclonal Antibody ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
E Coli ◽  
Tnf Α ◽  
Lps Activation ◽  
Necrosis Factor

The cytokines IL-1 and TNF-α are involved in inflammation and their production is stimulated by various agents, especially endotoxin (LPS). Here, using the human IL-1 receptor antagonist (IL-1RA) and a new monoclonal antibody (mAb 7F11) to rabbit TNF, the role of endogenous IL-l and TNF production in acute (3h) leukocyte (PMNL) recruitment to dermal inflammation in rabbits has been studied. IL-1RA inhibited by 27% the PMNL accumulation in reactions induced by killed Escherichia coli (p < 0.05) but not by LPS. The monoclonal antibody to TNF inhibited by 27% and 38% (p < 0.002) the PMNL accumulation in LPS and E. coli reactions respectively, but a combination of the mAb with IL-1RA was not more effective. Treatment of human umbilical vein endothelium with LPS for 3 h activated endothelium to induce PMNL transendothelial migration in vitro, which was not inhibited by IL-1RA, antibody to TNF-α, IL-1 or to IL-8. In conclusion, TNF and IL-1 may partially mediate acute PMNL infiltration in vivo to LPS and Gram negative bacteria, but there is a major IL-1/TNF independent mechanism, at least in dermal inflammation, which may be due to direct LPS activation of the microvasculature or perhaps the generation of cytokines other than IL-1 and TNF.

scholarly journals The role of TNF-alpha gene (-238G/A and -308G/A) polymorphisms in the etiology and pathogenesis of inflammatory bowel diseases in various ethnic groups

2019 ◽  
Vol 47 (6) ◽  
pp. 548-558
Author(s):  
I. V. Zhilin ◽  
E. Yu. Chashkova ◽  
A. A. Zhilina ◽  
B. S. Pushkarev ◽  
N. S. Korotaeva
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gene Polymorphism ◽  
Ethnic Groups ◽  
Small Sample ◽  
Tnf Α ◽  
Study Results ◽  
Inflammatory Bowel

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A  number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a  higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity.

scholarly journals Enterococcus faecium Alleviates Gut Barrier Injury in C57BL/6 Mice with Dextran Sulfate Sodium-Induced Ulcerative Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wei He ◽  
Weijie Ni ◽  
Junning Zhao
Keyword(s):  
Ulcerative Colitis ◽  
Enterococcus Faecium ◽  
Intestinal Flora ◽  
Underlying Mechanism ◽  
Mucosal Barrier ◽  
Microbiota Composition ◽  
Medicinal Value ◽  
Tnf Α ◽  
Inflammatory Bowel

The involvement of gut microbiota composition in ulcerative colitis is strongly supported by previous research. Growing evidence suggests that probiotic therapy protects against inflammatory bowel disease in animal models and patients. However, as a probiotic, the role of Enterococcus faecium (E. faecium) in UC remains unclear. Nevertheless, the potential mechanism of the protective effect of E. faecium remains unknown. In this study, a dextran sulphate sodium-induced (DSS-induced) colitis model was used to detect the underlying mechanism of E. faecium in maintaining gut homeostasis. ELISA was performed to detect the levels of cytokines (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, 454 pyrosequencing was used to investigate the microbiota composition in fecal samples. The results illustrate that E. faecium administration could prevent DSS-induced gut inflammation and intestinal flora imbalance. At the same time, the damage to intestinal mucosal barrier and tight junctions was partially repaired. These results demonstrate the preventive effect of E. faecium in DSS-induced intestinal injury. The present study provides new insights into the medicinal value of E. faecium for UC.

scholarly journals Effects of enriched environment and probiotics on the intestinal mucosal barrier and the brain-gut axis in rats with colorectal cancer

2020 ◽  
Author(s):  
Dun Liu ◽  
Wu Xian-Yi ◽  
Huang Si-Ting
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Mucosa ◽  
Muscle Thickness ◽  
Enriched Environment ◽  
Mucosal Barrier ◽  
Gut Peptides ◽  
Intestinal Mucosal Barrier ◽  
Tnf Α ◽  
Colorectal Cancer Patients

Abstract Background Enriched environment is a paradigm where animals are introduced to novel, complex, and stimulating surroundings that can protect the intestinal mucosal barrier and regulate the expression of brain-gut peptides. Probiotics can effectively protect the intestinal mucosal barrier and regulate brain-gut axis activity in colorectal cancer patients. This study assessed the effects of probiotics, enriched environment, and joint intervention on the intestinal mucosal barrier and brain-gut axis in rats with colorectal cancer. Methods We used a rat model of 1,2-dimethylhydrazine-induced colorectal cancer. Rats were housed in four different conditions for 2 weeks: enriched environment, probiotic,joint condition and normal condition. Each rat was weighed, and the intestinal mucosa and plasma levels of tumor TNF-α, IL-6, IL-10, ghrelin, CRF, occludin, BT, SIgA and the morphology of the intestinal mucosa were measured. Results enriched environment was beneficial regarding bacteria translation, plasma and intestinal mucosa levels of cytokines, plasma CRF levels, villi length and width of intestinal mucosa and hypothalamus ghrelin compared to probiotic (P < 0.05). There were no statistical differences between the enriched environment and the other groups regarding occludin, SIgA, muscle thickness or intestinal mucosa ghrelin (P > 0.05). Conclusions The effect of enriched environment was better than probiotic, especially in the intestinal mucosal immune and biological barrier in rats with colorectal cancer. However, the combination of the two was not as effective as enriched environment. In future studies, we can investigate the role of environment and probiotics in SIgA, intestinal mucosal mechanical barrier and body weight by extending the intervention time and enlarging the sample size.

scholarly journals Study of the Possible Alleviated Role of Atorvastatin on Irinotecan-Induced Lingual Mucosal Damage: Histological and Molecular Study

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Eetmad A. Arafat ◽  
S. M. Abo El-khair ◽  
A. Z. Elsamanoudy ◽  
Dalia A. Shabaan
Keyword(s):  
Gene Expression ◽  
Oral Mucositis ◽  
Molecular Study ◽  
Treated Group ◽  
Mucosal Damage ◽  
Ki 67 ◽  
Lingual Papillae ◽  
Study Results ◽  
Mrna Gene

Background. Oral mucositis is the most debilitating and troublesome adverse effect of irinotecan (CPT-11) treatment. It adversely affects the patient quality of life. The aim of this work was to study the histological, immunohistochemical, and molecular changes in the oral mucosa by CPT-11 and the possible alleviated role of atorvastatin. Methods. Rats were randomly divided into control, CPT-11-treated group, and CPT-11+ atorvastatin-treated group. At the end of the experiment, the anterior two-thirds of the tongue was dissected out and divided into two parts: one part for light microscopic examination and the second for molecular study. Results. CPT-11-treated group revealed loss of normal mucosal organization, areas of ulceration and inflammation, and loss of architecture of lingual papillae. A significant decrease in immunohistochemical and molecular gene expression of Ki-67 and antiapoptotic Bcl-2 levels was observed. A significant increase in NF-κB immunohistochemical and mRNA gene expression level and a nonsignificant increase in Nrf2 gene expression were detected. Coadministration of atorvastatin showed remarkable improvement in the histopathological picture with a significant increase in Ki-67 and Bcl-2, a significant decrease in NF-κB protein and gene expression, and a significant increase in Nrf2 gene expression. Conclusion. Atorvastatin substantially attenuates CPT-11-induced oral mucositis through the initiation of the antiapoptotic gene, modulation of the inflammatory, and antioxidant gene expression.

Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: plausible role of NF-κB, TNF-α and Bcl-2

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Ayaz Shahid ◽  
Rashid Ali ◽  
Nemat Ali ◽  
Syed Kazim Hasan ◽  
Summya Rashid ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biological Activities ◽  
Protective Effects ◽  
Oral Gavage ◽  
Carcinogenic Agent ◽  
Tnf Α ◽  
Lung Injuries ◽  
Ameliorative Effect ◽  
Apoptosis And Inflammation

Abstract: Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice.: Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation.: B(a)P enhanced lipid peroxidation, xanthine oxidase, H: The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity.

Bosentan, an endothelin receptor antagonist, ameliorates collagen-induced arthritis: the role of TNF-α in the induction of endothelin system genes

2012 ◽  
Vol 61 (4) ◽  
pp. 337-348 ◽  
Author(s):  
Paula B. Donate ◽  
Thiago M. Cunha ◽  
Waldiceu A. Verri ◽  
Cristina M. Junta ◽  
Flavia O. Lima ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Collagen Induced Arthritis ◽  
Endothelin System ◽  
Tnf Α

scholarly journals Infections in Patients with Hematological Cancer: Recent Developments

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 438-472 ◽  
Author(s):  
Susan N. O’Brien ◽  
Nicole M.A. Blijlevens ◽  
Tahsine H. Mahfouz ◽  
Elias J. Anaissie
Keyword(s):  
T Cell ◽  
Fungal Infections ◽  
Bone Marrow Involvement ◽  
Mucosal Damage ◽  
Invasive Fungal Infections ◽  
Mucosal Barrier ◽  
Treatment And Prevention ◽  
Hematologic Cancer ◽  
Recent Developments ◽  
Pathological Model

Abstract One of the most common complications involved in treating patients with hematologic cancer is infection. In many cases there are multiple factors that predispose these patients to infections such as neutropenia induced by therapy or bone marrow involvement, hypogammaglobulinemia, T-cell dysfunction, and mucosal damage. In addition, newer therapies have changed the spectrum of infection that is seen in these patients. In Section I, Dr. Blijlevens discusses mucosal damage as a major risk factor for complications of cytotoxic chemotherapy. She focuses on mucosal barrier injury (MBI) as manifest in the GI tract and will describe a pathological model to explain MBI, evaluate risk factors for development of this syndrome, explain the relationship between MBI and infection, and discuss treatment and prevention of this injury. Invasive fungal infections continue to represent a significant problem in patients with hematologic cancer. In Section II, Drs. Anaissie and Mahfouz review the latest developments in the diagnosis, prevention, and management of invasive fungal infections with a focus on a risk-adjusted approach to this problem. Finally, in Section III, Dr. O’Brien reviews infections associated with newer therapeutic regimens in hematologic cancers. The spectrum of infections has changed with the use of purine analogs and the advent of monoclonal antibodies. The profound T-cell suppression associated with these therapies has led to the emergence of previously rare infections such as cytomegalovirus. An approach to both prophylaxis and management of these infections is discussed.

scholarly journals Role of CD14 in Responses to Clinical Isolates of Escherichia coli: Effects of K1 Capsule Expression

2007 ◽  
Vol 75 (11) ◽  
pp. 5415-5424 ◽  
Author(s):  
Shalaka Metkar ◽  
Shanjana Awasthi ◽  
Erick Denamur ◽  
Kwang Sik Kim ◽  
Sophie C. Gangloff ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Necrosis Factor Alpha ◽  
Lethal Effects ◽  
E Coli ◽  
Tnf Α ◽  
Positive Isolate ◽  
K1 Capsule

ABSTRACT Severe bacterial infections leading to sepsis or septic shock can be induced by bacteria that utilize different factors to drive pathogenicity and/or virulence, leading to disease in the host. One major factor expressed by all clinical isolates of gram-negative bacteria is lipopolysaccharide (LPS); a second factor expressed by some Escherichia coli strains is a K1 polysaccharide capsule. To determine the role of the CD14 LPS receptor in the pathogenic effects of naturally occurring E. coli, the responses of CD14−/− and CD14+/+ mice to three different isolates of E. coli obtained from sepsis patients were compared; two isolates express both smooth LPS and the K1 antigen, while the third isolate expresses only LPS and is negative for K1. An additional K1-positive isolate obtained from a newborn with meningitis and a K1-negative isogenic mutant of this strain were also used for these studies. CD14−/− mice were resistant to the lethal effects of the K1-negative isolates. This resistance was accompanied by significantly lower levels of systemic tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in these mice than in CD14+/+ mice, enhanced clearance of the bacteria, and significantly fewer additional gross symptoms. In contrast, CD14−/− mice were as sensitive as CD14+/+ mice to the lethal effects of the K1-positive isolates, even though they had significantly lower levels of TNF-α and IL-6 than CD14+/+ mice. These studies show that different bacterial isolates can use distinctly different mechanisms to cause disease and suggest that new, nonantibiotic therapeutics need to be directed against multiple targets.

scholarly journals 1145. The Role of the Plasmid-Mediated Fluoroquinolone-Resistance (PMFQR) Genes As Resistance Mechanisms in Pediatric Infections due to Enterobacterales (Ent)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S664-S665
Author(s):  
Claire E Pitstick ◽  
Steven Marshall ◽  
Sreenivas Konda ◽  
Rachel L Medernach ◽  
T Nicholas Domitrovic ◽  
...  
Keyword(s):  
Healthcare Setting ◽  
Antibiotic Use ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Research Support ◽  
E Coli ◽  
Treatment And Prevention

Abstract Background Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug resistant (MDR) Ent infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies. Methods A case-control study of children (0-18 years) at 3 Chicago hospitals was performed. Cases had infections by FQ susceptible, 3rd generation cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR) Ent harboring a non or low level expressed PMFQR gene (PMFQS Ent). Controls had FQR infections due to 3GCR and/or CR Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed Rep-PCR, MLST, and E. coli phylogenetic grouping. Demographics; comorbidities; and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed. Results Of 170 G3CR and/or CR Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). 85 (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent were 4.3 and 6.2 years, respectively (p=NS). Of 23 PMFQS Ent, 53% were Klebsiella and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes in PMFQS Ent were blaSHV ESBL (44%); oqxB (57%) and aac-6’1b-cr (52%) and in PMFQR Ent were blaCTX-M-1 group (76%); aac-6’1b-cr (91%) and oqxA (17%). Multivariable regression analysis showed children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates with multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found. Conclusion Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, affecting therapeutic options and suggesting need for contact precautions. Control of PMFQS Ent infections in children will require validating sources and risk factors. Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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