• Authors: Dong, H. Y., Cui, Y., Zhang, B., Luo, Y., Wang, Y. X., Dong, M. Q., Liu, M. L., Zhao, P. T., Niu, W., Li, Z. C.
  • Year: 2017
  • Journal: Arch Biochem Biophys 634 47-56
  • Applications: in vivo / DNA / in vivo-jetPEI


Plasmid DNA-in vivo-jetPEI complexes were injected into mice by tail vein. Lung, heart and liver tissues were collected from sample mice of every group 12 h after LPS treatment for further study.


Controlling target gene expression is a vital step in the procedure of gene therapy upon acute lung injury (ALI). Excessive activation of nuclear factor-kappa B (NF-kappaB) has been the key point of the inflammation overwhelming process in onset of ALI. We designed and tested a variety of plasmid named pHSP70/IkappaBalpham which conditionally carries a mutant inhibitor of kappa B (IkappaB) transgene to regulate the activity of NF-kappaB signaling pathway in its response to an inflammatory stimulus that causes acute lung injury. Results recorded along our experiments showed that pHSP70/IkappaBalpham was able to control mutant IkappaB expression in RAW264.7 cells with reference to the level of inflammatory response induced by LPS, thereby inhibiting NF-kappaB activation and downstream inflammatory cytokine expression. Vivo experiments revealed that construction naming pHSP70/IkappaBalpham reduced LPS-induced lung injury and the secretion of inflammatory factors from lungs, hearts, and livers of sample mice in a LPS dose-dependent manner. In conclusion, the promoter heat shocking protein 70(HSP70) regulatory sequence of the construction was shown to drive mutant IkappaB expression so that its levels were positively associated with the dose of LPS used to induce acute lung injury. NF-kappaB activation and the downstream expression of inflammatory factors were therefore down-regulated in along an efficient path and ameliorating the damage as a consequence of LPS-induced acute lung injury.