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1.  Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release 
Nature immunology  2010;12(3):222-230.
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-18. Autophagic protein depletion promoted accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial ROS. Cytosolic mtDNA contributed to IL-1β and IL-18 secretion in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
doi:10.1038/ni.1980
PMCID: PMC3079381  PMID: 21151103
2.  Autophagy in cigarette smoke-induced chronic obstructive pulmonary disease 
The molecular and cellular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) remain incompletely understood. We have investigated the potential role of macro-autophagy, a cellular homeostatic mechanism, in COPD and cigarette smoke-induced lung-cell injury. Autophagy is a dynamic process for the turnover of organelles and proteins, which regenerates metabolic precursors through the lysosomal-dependent catabolism of cellular macromolecules. It is typically associated with survival pathways, especially in nutrient deficiency states. The role of autophagy in human diseases is less clear, and has been associated with both protective and detrimental consequences, depending on the disease model. While autophagy is considered cytoprotective, this process is often found in association with cell death, and the relationships between autophagy and cell death remain ambiguous. We have found elevated autophagy in COPD lung specimens, as well as in response to cigarette smoke exposure in vitro and in vivo. In our studies, the activation of autophagic proteins was associated with epithelial cell apoptosis in response to cigarette smoke, with pathogenic implications in COPD. Further studies are needed to determine the functional significance of autophagy in COPD and other diseases of the lung.
doi:10.1586/ers.10.61
PMCID: PMC3081520  PMID: 20923337
apoptosis; autophagy; chronic obstructive pulmonary disease; cigarette smoke; emphysema

Results 1-2 (2)