HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/L1248    most recent 00164.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Matsuda, N. Articles by Gando, S. Search for Related Content PubMed PubMed Citation Articles by Matsuda, N. Articles by Gando, S.

Therapeutic effect of in vivo transfection of transcription factor decoy to NF-B on septic lung in mice

¹Department of Anesthesiology and Critical Care Medicine, ²Department of Pharmacology, and ³Department of Biochemistry, Hokkaido University Graduate School of Medicine, and ⁴Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-8638, Japan

Submitted 6 May 2004 ; accepted in final form 27 July 2004

Nuclear factor-B (NF-B) plays a key role in regulating expression of several genes involved in the pathophysiology of endotoxic shock. We investigated whether in vivo introduction of synthetic double-stranded DNA with high affinity for the NF-B binding site could block expression of genes mediating pulmonary vascular permeation and thereby provide effective therapy for septic lung failure. Endotoxic shock was induced by an intravenous injection of 10 mg/kg Escherichia coli endotoxin in mice. We introduced NF-B decoy oligodeoxynucleotide (ODN) in vivo 1 h after endotoxic shock by using a gene transfer kit. At 10 h, blood samples were collected for measurement of histamine and for blood-gas analysis. Gene and protein expression levels of target molecules were determined by means of Northern and Western blot analyses, respectively. The transpulmonary flux of ¹²⁵I-labeled albumin was used as an index of lung vascular permeability. Administration of endotoxin caused marked increases in plasma histamine and gene and protein expressions of histidine decarboxylase, histamine H₁ receptors, and inducible nitric oxide synthase in lung tissues. Elevated lung vascular permeability was also found. Blood-gas analysis showed concurrent decreases in arterial PO₂, PCO₂, and pH. All of these events induced by endotoxin were significantly inhibited by transfection of NF-B decoy ODN but not by its mutated (scrambled) form (used as a control). Our results indicate for the first time the potential usefulness of NF-B decoy ODN for gene therapy of endotoxic shock.

gene therapy; histamine; histidine decarboxylase; histamine H₁ receptor; nitric oxide synthase; lung failure; endotoxic shock

This article has been cited by other articles:

				K. Kamiyama, N. Matsuda, S. Yamamoto, K.-i. Takano, Y. Takano, H. Yamazaki, S.-i. Kageyama, H. Yokoo, T. Nagata, N. Hatakeyama, et al. Modulation of glucocorticoid receptor expression, inflammation, and cell apoptosis in septic guinea pig lungs using methylprednisolone Am J Physiol Lung Cell Mol Physiol, December 1, 2008; 295(6): L998 - L1006. [Abstract] [Full Text] [PDF]

				V. Bezzerri, M. Borgatti, E. Nicolis, I. Lampronti, M. C. Dechecchi, I. Mancini, P. Rizzotti, R. Gambari, and G. Cabrini Transcription Factor Oligodeoxynucleotides to NF-{kappa}B Inhibit Transcription of IL-8 in Bronchial Cells Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 86 - 96. [Abstract] [Full Text] [PDF]

				C. L. S. George, K. L. Goss, D. K. Meyerholz, F. S. Lamb, and J. M. Snyder Surfactant-Associated Protein A Provides Critical Immunoprotection in Neonatal Mice Infect. Immun., January 1, 2008; 76(1): 380 - 390. [Abstract] [Full Text] [PDF]

				M. Rojas, C. R. Woods, A. L. Mora, J. Xu, and K. L. Brigham Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L333 - L341. [Abstract] [Full Text] [PDF]