Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: Although the expression of toll-like receptors (TLRs) on different types of human mesenchymal stem cells (hMSCs) has recently been reported, controversy remains regarding the presence of TLR4 as well as its engagement and impact on human Wharton's jelly-derived MSCs (hWJ-MSCs).
Methods: In the present study, the expression and role of TLR4 in hWJ-MSCs was investigated using a model of lipopolysaccharide (LPS). Proliferation, apoptosis, and the expression of paracrine factors in hWJ-MSCs primed with LPS were analysed.
Results: The expression of TLR4 was high at the RNA level but very low at the protein level. hWJ-MSCs responded to LPS stimulation and initiated a marked up-regulation of inflammatory cytokine (IL-1α, IL-1β, IL-6, and IL-8) production. Moreover, hWJ-MSCs LPS stimulation resulted in the up-regulation of indoleamine 2,3-dioxygenase [IDO]-1, Cox2, interferon [IFN]-β, and matrix metalloproteinase (MMP)-2 but a down-regulation of MMP-9, which affect the immunosuppressive potential of hWJ-MSCs.
Conclusions: These data suggest that LPS engagement shapes hWJ-MSCs and results in the production of pro-inflammatory cytokines and inhibitory immune mediators, showing TLR4 agonist induces the hWJ-MSCs polarization to a pro-inflammatory and immunosuppressive state, which may be beneficial for the exploration of the clinical potential of hWJ-MSCs.
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Source |
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http://dx.doi.org/10.1159/000354446 | DOI Listing |
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