Transforming Growth Factor Beta-Induced Is Essential for Endotoxin Tolerance Induced by a Low Dose of Lipopolysaccharide in Human Peripheral Blood Mononuclear Cells
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Abstract
Our prior study found that transforming growth factor beta-induced (TGFBI) is an important negative regulator in TLR-induced inflammation. However, whether TGFBI may affect inflammation during lipopolysaccharide (LPS)-induced endotoxin tolerance (ET) is still unclear.This study aimed to investigate whether TGFBI was involved in the mechanisms of ET in human through dampening nuclear factor-kappa B (NF-κB) mediated pathway. ET models of isolated healthy volunteers peripheral blood mononuclear cells (PBMCs) were established by pretreating with a low dose of LPS to observe the changes of TGFBI expression during ET induction, compared with ten healthy controls. Moreover, a vector-based short hairpin RNA expression system was used to specifically inhibit TGFBI expression to further explore its role in ET induction. The expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The responses to LPS were determined by the activation of NF-κB, the production of tumor necrosis factor-α (TNF-α) and Nitric Oxide (NO), which were analysed by enzyme-linked immuno sorbent assay (ELISA).The results showed that TGFBI expression in the ET group obviously increased; ET also led to a hyporesponse of PBMCs to LPS with less activation of NF-κB, less production of TNF-α and NO, as well as more expression of TGFBI than those of non-ET group. Moreover, the inhibitory effect was partly refracted in plasmid TGFBI short hairpin RNA (pTGFBI-shRNA) transfected PBMCs. Meanwhile, the absence of TGFBI caused abnormal enhancement of inflammatory cytokine production and it was involved in ET induction through dampening NF-κB mediated pathway.Therefore, TGFBI may be a new target for the clinical treatment of inflammatory disorders.
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| Files | ||
| Issue | Vol 14, No 3 (2015) | |
| Section | Original Article(s) | |
| Keywords | ||
| Endotoxin tolerance Lipopolysaccharide PBMCs TGFBI | ||
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