Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 14 3 2015 10 18 321 330 EN Yan Yang Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China Hanxiao Sun Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China Xiuying Li Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China Qing Ding Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China Pijin Wei Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China Jingguang Zhou Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China 2015 10 18 2015 10 18 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/574 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/574/459