The Involvement of Sphingolipids in Chronic Obstructive Pulmonary Diseases
Chronic obstructive pulmonary disease (COPD) includes a spectrum of conditions that have in common varying degrees of airflow obstruction, such as chronic bronchitis and emphysema. There is an increasing evidence of involvement of sphingolipids as key mol
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Contents 1 Introduction into the Pathogenesis of Chronic Obstructive Diseases of the Lung . . . . . . . . 2 The Role of Sphingolipids in COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Sphingolipid Involvement in Emphysema Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Ceramide-Induced Self-Amplification of Synthesis in the Lung . . . . . . . . . . . . . . . . . . . . 2.3 Ceramide-Induced Oxidative Stress Amplification in the Lung . . . . . . . . . . . . . . . . . . . . . 2.4 Death and Survival Signaling Induced by Sphingolipids in COPD . . . . . . . . . . . . . . . . . 2.5 Role of Sphingolipids in Alveolar Macrophage Dysfunction in COPD . . . . . . . . . . . . 2.6 Sphingolipid Responses in Hypoxic Lungs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Chronic Bronchitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Sphingolipid Involvement in Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Chronic obstructive pulmonary disease (COPD) includes a spectrum of conditions that have in common varying degrees of airflow obstruction, such as chronic bronchitis and emphysema. There is an increasing evidence of involvement of sphingolipids as key molecular mediators or biomarkers of disease in emphysema, chronic bronchitis, and more recently in asthma, another disease characterized by (reversible) airflow obstruction. Given the recognized central role of oxidative stress and inflammatory stimuli along with involvement of
I. Petrache (*) Division of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA Division of Pulmonary, Allergy, Critical Care and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Walther Hall-R3 C400, 980 W. Walnut Street, Indianapolis, IN 46202-5120, USA e-mail: [email protected] D.N. Petrusca Division of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA E. Gulbins and I. Petrache (eds.), Sphingolipids in Disease, Handbook of Experimental Pharmacology 216, DOI 10.1007/978-3-7091-1511-4_12, # Springer-Verlag Wien 2013
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immune responses, apoptosis, and tissue remodeling in the development of chronic obstructive lung diseases, it is not surprising that sphingolipids have been shown to play important role in their pathobiology. In particular the pro-apoptotic effects of ceramide were suspected as events in the lung destruction that occurs as a result of ap
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