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: 285/5/L1153    most recent 00084.2003v1 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 ISI 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 ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Salinas, D. Articles by Boggaram, V. Search for Related Content PubMed PubMed Citation Articles by Salinas, D. Articles by Boggaram, V.

Nitric oxide inhibits surfactant protein B gene expression in lung epithelial cells

Department of Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas 75708-3154

Submitted 24 March 2003 ; accepted in final form 29 July 2003

Surfactant protein B (SP-B) is an essential constituent of pulmonary surfactant. In a number of inflammatory diseases of the lung, elevated nitric oxide (NO) levels are associated with decreased SP-B levels, suggesting that reduced SP-B levels contribute to lung injury. In this study, we investigated the effects of NO on SP-B gene expression in H441 and MLE-12 cells, cell lines with characteristics of bronchiolar (Clara) and alveolar type II epithelial cells, respectively. Results show that NO donors decreased SP-B mRNA levels in a concentration- and time-dependent manner in H441 and MLE-12 cells. The NO donors also antagonized dexamethasone induction of SP-B mRNA in H441 cells. NO donor inhibition of SP-B mRNA was blocked by the transcriptional inhibitor 5,6-dichloro-1--D-ribofuranozyl-benzimidazole. NO donors decreased luciferase expression from a reporter plasmid containing -911/+41 bp of human SP-B 5'-flanking DNA in H441 and MLE-12 cells, indicating inhibitory effects on SP-B promoter activity. NO inhibition of SP-B mRNA levels was not blocked by LY-83583 and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively. Furthermore, cell-permeable cGMP analog 8-bromo-cGMP had no effect on SP-B mRNA levels. These data indicate that elevated NO levels negatively regulate SP-B gene expression by inhibiting gene transcription and that NO inhibits SP-B gene expression independently of cGMP levels. These data imply that reduced SP-B expression due to elevated NO levels can contribute to lung injury.

inflammation; transcription; lung injury; Clara cells; type II cells

This article has been cited by other articles:

				P. L. Ballard, J. D. Merrill, W. E. Truog, R. I. Godinez, M. H. Godinez, T. M. McDevitt, Y. Ning, S. G. Golombek, L. A. Parton, X. Luan, et al. Surfactant Function and Composition in Premature Infants Treated With Inhaled Nitric Oxide Pediatrics, August 1, 2007; 120(2): 346 - 353. [Abstract] [Full Text] [PDF]

				A. Das and V. Boggaram Proteasome dysfunction inhibits surfactant protein gene expression in lung epithelial cells: mechanism of inhibition of SP-B gene expression Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L74 - L84. [Abstract] [Full Text] [PDF]

				L. Sparkman, H. Chandru, and V. Boggaram Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L351 - L358. [Abstract] [Full Text] [PDF]

				J. W. Lee, R. F. Gonzalez, C. J. Chapin, J. Busch, J. R. Fineman, and J. A. Gutierrez Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L950 - L957. [Abstract] [Full Text] [PDF]

				L. Sparkman and V. Boggaram Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L764 - L773. [Abstract] [Full Text] [PDF]