TY - JOUR
T1 - Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke
AU - Cavarra, Eleonora
AU - Fardin, Paolo
AU - Fineschi, Silvia
AU - Ricciardi, Annamaria
AU - De Cunto, Giovanna
AU - Sallustio, Fabio
AU - Zorzetto, Michele
AU - Luisetti, Maurizio
AU - Pfeffer, Ulrich
AU - Lungarella, Giuseppe
AU - Varesio, Luigi
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Antioxidant defenses
KW - Cigarette smoke susceptibility
KW - Emphysema
KW - Microarrays
KW - Mouse strains
UR - http://www.scopus.com/inward/record.url?scp=64249111192&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64249111192&partnerID=8YFLogxK
U2 - 10.1152/ajplung.90382.2008
DO - 10.1152/ajplung.90382.2008
M3 - Article
C2 - 19118092
AN - SCOPUS:64249111192
VL - 296
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 3
ER -