Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background & Aims: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. It is unclear how infiltrating leukocytes affect NASH-development. Our study aims to investigate the role of the homing/receptor, pair mucosal addressin cell adhesion molecule-1 (MAdCAM-1)/β-Integrin, on immune cell recruitment and disease progression in a steatohepatitis model.
Methods: Constitutive β-Integrin deficient (β) and MAdCAM-1 deficient (MAdCAM-1) mice were fed a high fat diet (HFD) for 26weeks or methionine-choline-deficient-diet (MCD) for 4weeks.
Results: β mice displayed earlier and more progressive steatohepatitis during HFD- and MCD-treatment, while MAdCAM-1 mice showed less histomorphological changes. The anti-oxidative stress response was significantly weaker in β mice as reflected by a significant downregulation of the transcription factors nuclear-factor(erythroid-derived 2)-like 2 (Nrf2) and heme-oxigenase-1 (HO-1). Additionally, stronger dihydroethidium-staining revealed an increased oxidative stress response in β animals. In contrast, MAdCAM-1 mice showed an upregulation of the anti-oxidative stress response. β animals exhibited stronger hepatic infiltration of inflammatory cells, especially neutrophils, reflecting earlier steatohepatitis initiation. Expression of regulatory T cell (T) markers as well as numbers of anti-inflammatory macrophages was significantly enhanced in MAdCAM-1 mice. Those changes finally resulted in earlier and stronger collagen accumulation in β mice, whereas MAdCAM-1 mice were protected from fibrosis initiation.
Conclusions: Adhesion molecule mediated effector cell migration contributes to the outcome of steatohepatitis in the HFD- and the MCD model. While MAdCAM-1 promotes steatohepatitis, β-Integrin unexpectedly exerts protective effects. β mice show earlier steatohepatitis initiation and significantly stronger fibrosis progression. Accordingly, the interaction of β-Integrins and their receptor MAdCAM-1 provide novel targets for therapeutic interventions in steatohepatitis.
Lay Summary: The mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is expressed in livers upon diet-induced non-alcoholic steatohepatitis (NASH). Loss of MAdCAM-1 has beneficial effects regarding the development of NASH - manifested by reduced hepatic oxidative stress and decreased inflammation. In contrast, β-Integrin-deficiency results in increased steatohepatitis.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.jhep.2017.02.001 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!