title: Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke.
abstract: We have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57BL/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, whereas ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype. The three strains of mice were exposed to smoke from three cigarettes per day, 5 days/wk, for 4 wk. Microarray analysis was carried out on total RNA extracted from the lung using the Affymetrix platform. Cigarette smoke modulates several clusters of genes (i.e., proemphysematous, acute phase response, and cell adhesion) in smoke-sensitive DBA/2 or C57BL/6J strains, but the same genes are not altered by smoke in ICR resistant mice. Only a few genes were commonly modulated by smoke in the three strains of mice. This pattern of gene expression suggests that the response to smoke is strain-dependent and may involve different molecular signaling pathways. Real-time quantitative PCR was used to verify the pattern of modulation of selected genes and their potential biological relevance. We conclude that gene expression response to smoke is highly dependent on the mouse genetic background. We speculate that the definition of gene clusters associated, to various degrees, with mouse susceptibility or resistance to smoke may be instrumental in defining the molecular basis of the individual response to smoke-induced lung injury in humans.
authors.affiliation: Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Siena, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cavarra
authors.forename: Paolo
authors.initials: P
authors.lastname: Fardin
authors.forename: Silvia
authors.initials: S
authors.lastname: Fineschi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ricciardi
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Cunto
authors.forename: Fabio
authors.initials: F
authors.lastname: Sallustio
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfeffer
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lungarella
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics* / Q000473:pathology; D013045:Species Specificity
chemical_list: D017931:DNA Primers