Prenatal Cigarette Smoke Decreases Lung cAMP and Increases Airway Hyperresponsiveness

Abstract

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.

Smoke Extract Impairs Adenosine Wound Healing. Implications of Smoke-Generated Reactive Oxygen Species

“…Smoke extract significantly reduced A 2A -stimulated PKA, and was mediated by the smoke extract reduction of cAMP concentrations. These data further support earlier studies that revealed how cigarette smoke exposure decreases cAMP concentrations (49). Cigarette smoke has also been documented to activate PKC (50), and considering the differential roles of PKA and PKC, we investigated the smoke extract-mediated activation of PKC, and found a robust activation of PKC in A 2A -stimulated wounded epithelial cells exposed to smoke extract.…”

Maternal smoking during pregnancy induces airway remodelling in mice offspring

“…In mouse offspring exposed to maternal smoking in utero, MCh responsiveness was reportedly associated with a decreased presence of cyclic AMP in lung tissue [18]. This is of interest, since cyclic AMP is involved in relaxation of smooth muscle in the airway.…”

In UteroExposure to Second-Hand Smoke Aggravates the Response to Ovalbumin in Adult Mice

“…We used BALB/c mice for three reasons: (1) BALB/c mice are a well-accepted strain for asthma studies (4-7, 13); (2) a high correlation has been reported for these mice between Penh values and lung resistance (14)(15)(16), and (3) we have established laboratory protocols in BALB/c mice for investigating the effects of in utero SHS exposure on adult lung responses to environmental irritants (3,11). Control groups without OVA challenge were not included in the study because our previous studies revealed that adult mice exposed in utero to SHS, but not exposed as adults to environmental stressors, do not exhibit signs of inflammation compared with the AIR mice (3,11).…”