Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema

作者：Miller Marina; Pham Alexa; Cho Jae Youn; Rosenthal Peter; Broide David H^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2010, 299(6): L834-L842.

DOI：10.1152/ajplung.00326.2009

• macrophage
• neutrophil
• tumor necrosis factor-alpha
• keratinocyte-derived
• chemokine

Miller M, Pham A, Cho JY, Rosenthal P, Broide DH. Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema. Am J Physiol Lung Cell Mol Physiol 299: L834-L842, 2010. First published October 8, 2010; doi:10.1152/ajplung.00326.2009.-Adiponectin is a cytokine with both proinflammatory and antiinflammatory properties that is expressed in epithelial cells in the airway in chronic obstructive pulmonary disease-emphysema (COPD-E). To determine whether adiponectin modulates levels of lung inflammation in tobacco smoke-induced COPD-E, we used a mouse model of COPD-E in which either adiponectin-deficient or wild-type (WT) mice were exposed to tobacco smoke for 6 mo. Outcomes associated with tobacco smoke-induced COPD-E were quantitated including lung inflammation [bronchoalveolar lavage (BAL) and total and differential cell count], lung mediators of inflammation (cytokines and chemokines), air space enlargement (i.e., linear intercept), and lung tissue elastance) in the different groups of mice. Whereas exposure of WT mice to tobacco smoke for 6 mo induced significant lung inflammation (increased total BAL cells, neutrophils, and macrophages), adiponectin-deficient mice had minimal BAL inflammation when exposed to tobacco smoke for 6 mo. In addition, whereas chronic tobacco-exposed WT mice had significantly increased levels of lung mediators of inflammation [i.e., TNF-alpha, keratinocyte-derived chemokine (KC), and adiponectin] as well as significantly increased air space enlargement (increased linear intercept) and decreased tissue elastance, exposure of adiponectin-deficient mice to chronic tobacco smoke resulted in no further increase in lung mediators, air space enlargement, or tissue elastance. In vitro studies demonstrated that BAL macrophages derived from adiponectin-deficient mice incubated in media containing tobacco smoke expressed minimal TNF-alpha or KC compared with BAL macrophages from WT mice. These studies suggest that adiponectin plays an important proinflammatory role in tobacco smoke-induced COPD-E.

• 出版日期2010-12