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The gene expression signature of chronic marijuana use

ABSTRACT: Alveolar macrophage (AM) gene expression studies in cigarette smokers have identified dysregulated molecular pathways relevant to clinical outcomes. However, parallel studies in cannabis smokers are limited, despite marijuana’s increasing public health relevance. We performed the first genome-wide gene expression analysis from the lungs of marijuana smokers to test the hypothesis that marijuana is associated with changes in AM gene expression that may contribute to altered immune function. AMs from bronchoalveolar lavage from 15 marijuana smokers, 16 cigarette smokers, and 10 non-smokers were isolated for RNA sequencing. We performed differential expression analysis to identify genes that differed on average between smoking groups, with emphasis on genes associated with M1/M2 macrophage polarization and immunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155213 | GEO | 2021/10/02

REPOSITORIES: GEO

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Project description:Cigarette smoking is the leading cause of the respiratory diseases collectively known as chronic obstructive pulmonary disease (COPD). While the pathogenesis of COPD is complex, there is abundant evidence that alveolar macrophages (AM) play an important role. Based on the concept that COPD is a slow-progressing disorder likely involving multiple mediators released by AM activated by cigarette smoke, the present study focuses on the identification of previously unrecognized genes that may be linked to early events in the molecular pathogenesis of COPD, as opposed to factors associated with the presence of disease. To accomplish this, microarray analysis using Affymetrix microarrays was used to carry out an unbiased survey of the differences in gene expression profiles in the AM of phenotypically normal, ~20 pack-yr smokers compared to healthy non-smokers. Although smoking did not alter the global gene expression pattern of AM, 75 genes were modulated by smoking, with 40 genes up-regulated and 35 down-regulated in the AM of smokers compared to non-smokers. Most of these genes belong to the functional categories of immune/inflammatory response, cell adhesion and extracellular matrix, proteolysis and antiproteolysis, lysosomal function, antioxidant-related, signal transduction and regulation of transcription. Of these 75 genes, 69 have not been previously recognized to be up- or down-regulated in alveolar macrophages in association with smoking or COPD, including genes coding for proteins belonging to all of the above categories, and others belonging to various functional categories or of unknown function. These observations suggest that gene expression responses of alveolar macrophages associated with the stress of cigarette smoking are more complex than previously thought, and offer a variety of new insights into the complex pathogenesis of smoking-induced lung diseases. Experiment Overall Design: 5 non smokers and 5 smokers Experiment Overall Design: Alveolar macrophages were obtained from bronchoalveolar lavage

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The gene expression signature of chronic marijuana use

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