Transforming Growth Factor Beta-Induced Is Essential for Endotoxin Tolerance Induced by a Low Dose of Lipopolysaccharide in Human Peripheral Blood Mononuclear Cells

• Main Authors: Yan Yang, Hanxiao Sun, Xiuying Li, Qing Ding, Pijin Wei, Jingguang Zhou
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2015-10-01
• Series: Iranian Journal of Allergy, Asthma and Immunology
• Subjects: Endotoxin tolerance; Lipopolysaccharide; PBMCs; TGFBI
• Online Access: https://ijaai.tums.ac.ir/index.php/ijaai/article/view/574

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.