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      Modulation of inflammation by autophagy: Consequences for human disease

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          ABSTRACT

          Autophagy and inflammation are 2 fundamental biological processes involved in both physiological and pathological conditions. Through its crucial role in maintaining cellular homeostasis, autophagy is involved in modulation of cell metabolism, cell survival, and host defense. Defective autophagy is associated with pathological conditions such as cancer, autoimmune disease, neurodegenerative disease, and senescence. Inflammation represents a crucial line of defense against microorganisms and other pathogens, and there is increasing evidence that autophagy has important effects on the induction and modulation of the inflammatory reaction; understanding the balance between these 2 processes may point to important possibilities for therapeutic targeting. This review focuses on the crosstalk between autophagy and inflammation as an emerging field with major implications for understanding the host defense on the one hand, and for the pathogenesis and treatment of immune-mediated diseases on the other hand.

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          Most cited references130

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          On the origin of cancer cells.

          O WARBURG (1956)
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            The role of Atg proteins in autophagosome formation.

            Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.
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              Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

              Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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                Author and article information

                Journal
                Autophagy
                Autophagy
                KAUP
                kaup20
                Autophagy
                Taylor & Francis
                1554-8627
                1554-8635
                February 2016
                29 July 2015
                29 July 2015
                : 12
                : 2
                : 245-260
                Affiliations
                [a ]Department of Internal Medicine, Radboud University Medical Center , Nijmegen, The Netherlands
                [b ]Division of Endocrinology, Radboud University Medical Center , Nijmegen, The Netherlands
                [c ]Radboud Center for Infectious Diseases, Radboud University Medical Center , Nijmegen, The Netherlands
                Author notes
                Article
                1071759
                10.1080/15548627.2015.1071759
                4836004
                26222012
                60a0a8a8-4215-4604-94ab-36537f93f2be
                © 2016 The Author(s). Published with license by Taylor & Francis.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 9 February 2015
                : 18 June 2015
                : 8 July 2015
                Page count
                Figures: 4, Tables: 0, References: 199, Pages: 16
                Categories
                Review

                Molecular biology
                autoimmune diseases,autoinflammatory diseases,autophagy,carcinogenesis,infectious diseases,inflammation

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