Cigarette smoke (CS) and genetic susceptibility are the main risk factors for the development of chronic obstructive pulmonary disease (COPD). With respect to the pathogenesis of COPD, one important hypothesis is the imbalance between oxidants and antioxidants in the airways and parenchyma. Animal studies have shown that C57Bl/6J mice are sensitive to CS and develop emphysema, while ICR mice are not. To investigate the potential factors responsible for the different susceptibility of ICR and C57Bl/6J mice to CS, we evaluated in alveolar macrophages (AMs) isolated from these strains of mice the possible mechanisms involved in the oxidative and inflammatory responses induced by CS. Control C57Bl/6J AMs showed a higher baseline production of ROS and H2O2 with lower baseline levels of GSH, Nrf2, HO-1 and GPX2. This was associated with reduced HDAC2 expression, activation of NF-kB and higher basal levels of TNF-a and IL-6. After cigarette smoke extract (CSE) exposure, proinflammatory cytokines and matrix metalloproteases (MMPs) were increased in C57Bl/6J, but not in ICR AMs. CSE induced a decrease in HDAC2 protein levels both in C57Bl/6J and ICR AMs however, the level of HDAC2 was significantly lower in C57Bl/6 than in ICR AMs. Furthermore, CSE enhanced NF-kB dependent cytokine release only in C57Bl/6J AMs. We then suggest that an imbalance in oxidative stress decreases HDAC2 levels and facilitates NF-B binding resulting in a proinflammatory response in C57Bl/6J but not in ICR AMs. These results could contribute to the understanding of the different susceptibility to CS of these strains of mice.

Gardi, C., Vecchio, D., Arezzini, B., Pecorelli, A., Martorana, P.A., Valacchi, G. (2010). Oxidative stress in alveolar macrophages from mice with different reactivity to cigarette smoke. In Atti di 7° Indo- Italian Workshop on Chemistry and Biology of Antioxidants (pp.12-12).

Oxidative stress in alveolar macrophages from mice with different reactivity to cigarette smoke

Gardi, C.;
2010-01-01

Abstract

Cigarette smoke (CS) and genetic susceptibility are the main risk factors for the development of chronic obstructive pulmonary disease (COPD). With respect to the pathogenesis of COPD, one important hypothesis is the imbalance between oxidants and antioxidants in the airways and parenchyma. Animal studies have shown that C57Bl/6J mice are sensitive to CS and develop emphysema, while ICR mice are not. To investigate the potential factors responsible for the different susceptibility of ICR and C57Bl/6J mice to CS, we evaluated in alveolar macrophages (AMs) isolated from these strains of mice the possible mechanisms involved in the oxidative and inflammatory responses induced by CS. Control C57Bl/6J AMs showed a higher baseline production of ROS and H2O2 with lower baseline levels of GSH, Nrf2, HO-1 and GPX2. This was associated with reduced HDAC2 expression, activation of NF-kB and higher basal levels of TNF-a and IL-6. After cigarette smoke extract (CSE) exposure, proinflammatory cytokines and matrix metalloproteases (MMPs) were increased in C57Bl/6J, but not in ICR AMs. CSE induced a decrease in HDAC2 protein levels both in C57Bl/6J and ICR AMs however, the level of HDAC2 was significantly lower in C57Bl/6 than in ICR AMs. Furthermore, CSE enhanced NF-kB dependent cytokine release only in C57Bl/6J AMs. We then suggest that an imbalance in oxidative stress decreases HDAC2 levels and facilitates NF-B binding resulting in a proinflammatory response in C57Bl/6J but not in ICR AMs. These results could contribute to the understanding of the different susceptibility to CS of these strains of mice.
2010
Gardi, C., Vecchio, D., Arezzini, B., Pecorelli, A., Martorana, P.A., Valacchi, G. (2010). Oxidative stress in alveolar macrophages from mice with different reactivity to cigarette smoke. In Atti di 7° Indo- Italian Workshop on Chemistry and Biology of Antioxidants (pp.12-12).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/26577
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