E Felley-Bosco, S Ambs, CJ Lowenstein, LK Keefer and CC Harris
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland.

Two major roles have been defined for nitric oxide (NO): cell-cell communication mediated by the stimulation of cyclic guanosine 3',5'- monophosphate (cGMP) synthesis and cytotoxicity by direct or indirect interaction of the free radical NO with cellular targets. Thus, pathologic states might result from an alteration of NO pathways, e.g., by deregulated activity of NO synthase. To investigate this hypothesis, we introduced the murine-inducible NO synthase (iNOS) sequence into immortalized human bronchial epithelial cells (BEAS-2B). iNOS activity, measured by conversion of [14C]arginine to [14C]citrulline in the presence of 1 mM EGTA, was higher than 100 pmol/min/mg protein in early passages of iNOS-transfected cells but decreased with cell subculturing. No iNOS activity could be detected in control vector- transfected cells. NO stimulated cGMP production in iNOS-transfected cells, and this effect was inhibited by the iNOS inhibitor NG- monomethyl-L-arginine. In addition, NO production induced c-fos expression and did not interfere with clonal cell growth. These results suggest that BEAS-2B cells constitute a suitable model to study the consequences of iNOS activity on signal transduction pathways in bronchial epithelium.

This article has been cited by other articles:

				Y. Chen, S. Zhuang, S. Cassenaer, D. E. Casteel, T. Gudi, G. R. Boss, and R. B. Pilz Synergism between Calcium and Cyclic GMP in Cyclic AMP Response Element-Dependent Transcriptional Regulation Requires Cooperation between CREB and C/EBP-{beta} Mol. Cell. Biol., June 15, 2003; 23(12): 4066 - 4082. [Abstract] [Full Text] [PDF]

				D. E. Casteel, S. Zhuang, T. Gudi, J. Tang, M. Vuica, S. Desiderio, and R. B. Pilz cGMP-dependent Protein Kinase Ibeta Physically and Functionally Interacts with the Transcriptional Regulator TFII-I J. Biol. Chem., August 23, 2002; 277(35): 32003 - 32014. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, D. P. Riley, A. P. Caputi, and D. Salvemini Antioxidant Therapy: A New Pharmacological Approach in Shock, Inflammation, and Ischemia/Reperfusion Injury Pharmacol. Rev., March 1, 2001; 53(1): 135 - 159. [Abstract] [Full Text] [PDF]

				E. Felley-Bosco, F. C. Bender, F. Courjault-Gautier, C. Bron, and A. F. G. Quest Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells PNAS, December 8, 2000; (2000) 250406797. [Abstract] [Full Text]

				H. E. MARSHALL, K. MERCHANT, and J. S. STAMLER Nitrosation and oxidation in the regulation of gene expression FASEB J, October 1, 2000; 14(13): 1889 - 1900. [Abstract] [Full Text]

				T. GUDI, G. K.-P. HONG, A. B. VAANDRAGER, S. M. LOHMANN, and R. B. PILZ Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase FASEB J, December 1, 1999; 13(15): 2143 - 2152. [Abstract] [Full Text]

				T. Jilling, I. Y. Haddad, S. H. Cheng, and S. Matalon Nitric oxide inhibits heterologous CFTR expression in polarized epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L89 - L96. [Abstract] [Full Text] [PDF]

				S. D. Idriss, T. Gudi, D. E. Casteel, V. G. Kharitonov, R. B. Pilz, and G. R. Boss Nitric Oxide Regulation of Gene Transcription via Soluble Guanylate Cyclase and Type I cGMP-dependent Protein Kinase J. Biol. Chem., April 2, 1999; 274(14): 9489 - 9493. [Abstract] [Full Text] [PDF]

				D. C. Thompson, S. E. Porter, A. K. Bauer, K. C. Das, B. Ou, L. Dwyer-Nield, C. W. White, and A. M. Malkinson Cytokine-induced nitric oxide formation in normal but not in neoplastic murine lung epithelial cell lines Am J Physiol Lung Cell Mol Physiol, June 1, 1998; 274(6): L922 - L932. [Abstract] [Full Text] [PDF]

				X. Y. LI, K. DONALDSON, and W. MACNEE Lipopolysaccharide-induced Alveolar Epithelial Permeability . The Role of Nitric Oxide Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): 1027 - 1033. [Abstract] [Full Text] [PDF]

				C. L. Hartsfield, J. Alam, J. L. Cook, and A. M. K. Choi Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide Am J Physiol Lung Cell Mol Physiol, November 1, 1997; 273(5): L980 - L988. [Abstract] [Full Text] [PDF]

				T. Gudi, I. Huvar, M. Meinecke, S. M. Lohmann, G. R. Boss, and R. B. Pilz Regulation of Gene Expression by cGMP-dependent Protein Kinase J. Biol. Chem., March 1, 1996; 271(9): 4597 - 4600. [Abstract] [Full Text] [PDF]

				E. Felley-Bosco, F. C. Bender, F. Courjault-Gautier, C. Bron, and A. F. G. Quest Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells PNAS, December 19, 2000; 97(26): 14334 - 14339. [Abstract] [Full Text] [PDF]