Transforming growth factor beta-induced is essential for endotoxin tolerance induced by a low dose of lipopolysaccharide in human peripheral blood mononuclear cells

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. copyright © spring 2015,iran j allergy asthma immunol. all rights reserved.