title: Transforming Growth Factor Beta-Induced Is Essential for Endotoxin Tolerance Induced by a Low Dose of Lipopolysaccharide in Human Peripheral Blood Mononuclear Cells.
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.
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Hanxiao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Pijin
authors.initials: P
authors.lastname: Wei
authors.affiliation: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Jingguang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000502:physiology; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099222:betaIG-H3 Protein
keywords: Endotoxin tolerance; Lipopolysaccharide; PBMCs; TGFBI