The resulting loss of TJ- and AJ stability may subsequently lead to loss of barrier function of the epithelium. As PCDH1 was previously reported to have a role in cell-cell adhesion, we hypothesize that CS-induced decrease in Pcdh1 levels might contribute to the reduced epithelial barrier function after CS exposure. Since we only provide data on the association of reduced Pcdh1 expression levels after CS exposure, future mechanistic studies in for instance Pcdh1 (+)-JQ1 1268524-70-4 knock-out mice will need to address whether Pcdh1 has any functional role in the CS-induced response by the airway epithelium, including loss of epithelial barrier function. In conclusion, our data show that Pcdh1 is strongly conserved between mouse and man. Furthermore, our data are the first to show that Pcdh1 mRNA expression is strongly regulated by CS-exposure, both in acute and chronic exposure models. Future studies on the function of Protocadherin-1, using novel knockout and/or transgenic approaches, and its interaction with environmental factors such as CS exposure are required to provide novel insights into the origins of airway hyperresponsiveness. Cigarette smoking is one of the leading causes of morbidity and mortality globally. According to one report, approximately 4.9 million people died around the world in 2007 as a result of smoking. A great interest of researchers is assessing the influence of chronic cigarette smoking on the human brain. Chronic cigarette smoking has been associated with structural changes in several key brain regions, including the medial frontal cortex, thalamus, insula, parietal cortex, anterior cingulate cortex, and middle cingulate cortex. Consequently, smokers have several difficulties in completing cognitive tasks, such as working memory, delayed reward, and cognitive control tasks. A growing body of evidence suggests that several regions of the brain display structural changes as a result of chronic cigarette smoking. Gons et al. used diffusion tensor imaging to show that a history of cigarette smoking could be associated with the reduced microstructural integrity of white matter. Compared with nonsmokers, chronic cigarette smokers have higher fractional anisotropy in the bilateral superior longitudinal fasciculus, which is a major WM pathway of frontoparietal tracts. Smokers also have higher FA in the prefrontal WM, cingulum cortex, and genu corpus callosum than nonsmokers. Other studies have found that smokers have smaller gray matter volumes in the thalamus, medial frontal cortex, cingulate cortex, and bilateral prefrontal cortex than non-smokers through voxel-based morphometry. The gray matter densities in the bilateral prefrontal cortex, orbitofrontal cortex, occipital lobe, and the temporal lobe were also found to decrease for smokers. Aside from changes in the brain structures of smokers, the influence of nicotine on brain functions after acute smoking is also of interest. In an early functional magnetic resonance imaging study, Stein et al. found increased activation in the insula, frontal lobes, and amygdala after cumulative intravenous nicotine administration in cigarette smokers. Another study used fMRI to investigate the acute effects of nicotine on smokers and reported an improvement in the performance of smokers at a visual attention task after nicotine administration due to increased activation in the insula, frontal gyrus, caudate, and thalamus. Recently, several studies have examined the nicotine effect on large-scale brain networks. Hahn et al. used event-related fMRI to investigate the influence of nicotine on smokers’ attention and found that nicotine induced deactivation in the default mode network and improved attention performance in smokers. Cole et al. investigated the effects of nicotine replacement on abstinent smokers through resting-state fMRI ; the therapeutic effect of nicotine replacement on cognitive withdrawal symptoms was associated with an enhanced inverse coupling between the executive control network and DMN. Another study which used rs-fMRI also showed that smokers exhibited reduced connectivity in DMN regions and increased activity in the network related to attention after nicotine administration. These results showed that nicotine was associated with decreased activity in DMN regions and increased activity in the regions related to executive control and attention. Nicotine, which is a main chemical substance in cigarettes, can alter neural activity by activating nicotinic cholinergic receptors. However, information on the effects of acute cigarette smoking on neural circuits remains insufficient. Increasing evidence has shown that distributed neural circuits in the brain exhibit spontaneous activity while people are at rest. These slow frequency fluctuations in brain activity are temporally correlated within functionally related networks. Such evidence provides an opportunity to investigate and characterize neural circuit abnormalities in smokers. However, no study has investigated global functional connectivity patterns after acute cigarette smoking, although prior findings constitute important advances in our understanding of addiction to smoking. Such a global, data-driven approach is important to comprehensively examine the changes in global brain connectivity after acute cigarette smoking.