This Article Full Text Full Text (PDF) All Versions of this Article: 200211-1262OCv1 168/3/342    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Singh, S. P. Articles by Sopori, M. L. Search for Related Content PubMed PubMed Citation Articles by Singh, S. P. Articles by Sopori, M. L.

Prenatal Cigarette Smoke Decreases Lung cAMP and Increases Airway Hyperresponsiveness

Respiratory Immunology and Asthma Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico; and VA Medical Center and Medical College of Wisconsin, Milwaukee, Wisconsin

Correspondence and requests for reprints should be addressed to Mohan L. Sopori, Ph.D., Respiratory and Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108. E-mail: msopori{at}lrri.org

Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.

Key Words: asthma • phosphodiesterase-4D • Aspergillus fumigatus • airway responsiveness

This article has been cited by other articles:

				S. P. Singh, N. C. Mishra, J. Rir-sima-ah, M. Campen, V. Kurup, S. Razani-Boroujerdi, and M. L. Sopori Maternal Exposure to Secondhand Cigarette Smoke Primes the Lung for Induction of Phosphodiesterase-4D5 Isozyme and Exacerbated Th2 Responses: Rolipram Attenuates the Airway Hyperreactivity and Muscarinic Receptor Expression but Not Lung Inflammation and Atopy J. Immunol., August 1, 2009; 183(3): 2115 - 2121. [Abstract] [Full Text] [PDF]

				M. J. Blacquiere, W. Timens, B. N. Melgert, M. Geerlings, D. S. Postma, and M. N. Hylkema Maternal smoking during pregnancy induces airway remodelling in mice offspring Eur. Respir. J., May 1, 2009; 33(5): 1133 - 1140. [Abstract] [Full Text] [PDF]

				T. Mauad, D. H. R. F. Rivero, R. C. de Oliveira, A. J. de Faria Coimbra Lichtenfels, E. T. Guimaraes, P. A. de Andre, D. I. Kasahara, H. M. de Siqueira Bueno, and P. H. N. Saldiva Chronic Exposure to Ambient Levels of Urban Particles Affects Mouse Lung Development Am. J. Respir. Crit. Care Med., October 1, 2008; 178(7): 721 - 728. [Abstract] [Full Text] [PDF]

				R. T. Cohen, G. J. Canino, H. R. Bird, S. Shen, B. A. Rosner, and J. C. Celedon Area of Residence, Birthplace, and Asthma in Puerto Rican Children Chest, May 1, 2007; 131(5): 1331 - 1338. [Abstract] [Full Text] [PDF]

				Q. Song, J. W. Cole, J. R. O'Connell, O. C. Stine, M. Gallagher, W. H. Giles, B. D. Mitchell, M. A. Wozniak, B. J. Stern, J. D. Sorkin, et al. Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study Hum. Mol. Genet., August 15, 2006; 15(16): 2468 - 2478. [Abstract] [Full Text] [PDF]

				J. Min, Y.-M. Jin, J.-S. Moon, M.-S. Sung, S. Ahn Jo, and I. Jo Hypoxia-Induced Endothelial NO Synthase Gene Transcriptional Activation Is Mediated Through the Tax-Responsive Element in Endothelial Cells Hypertension, June 1, 2006; 47(6): 1189 - 1196. [Abstract] [Full Text] [PDF]

				H.-F. Tang, Y.-H. Song, J.-C. Chen, J.-Q. Chen, and P. Wang Upregulation of Phosphodiesterase-4 in the Lung of Allergic Rats Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 823 - 828. [Abstract] [Full Text] [PDF]

				J. P. Bradley, L. B. Bacharier, J. Bonfiglio, K. B. Schechtman, R. Strunk, G. Storch, and M. Castro Severity of Respiratory Syncytial Virus Bronchiolitis Is Affected by Cigarette Smoke Exposure and Atopy Pediatrics, January 1, 2005; 115(1): e7 - e14. [Abstract] [Full Text] [PDF]

				M. J. Tobin Pediatrics, Surfactant, and Cystic Fibrosis in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 277 - 287. [Full Text] [PDF]