caa a22 4500 445795719 CHVBK 20180317145124.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10620-011-1692-0 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1692-0 Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis [Elektronische Daten] [Violeta Arsenescu, Meena Narasimhan, Tuna Halide, Ray Bressan, Chiara Barisione, Donald Cohen, Willem de Villiers, Razvan Arsenescu] Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn's disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter—LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. Springer Science+Business Media, LLC, 2011 Adiponectin nationallicence Inflammatory bowel disease nationallicence Mammalian adiponectin homolog nationallicence PPARγ agonists nationallicence Dendritic cells nationallicence Inflammatory bowel disease nationallicence Ao : Angiotensinogen nationallicence ACE : Angiotensin converting enzyme nationallicence AN : Adiponectin nationallicence AT1a : Angiotensin receptor 1a nationallicence BIP : Endoplasmic reticulum-binding protein (Hsp70) nationallicence CASP12 : Caspase 12 nationallicence CCR2 : Chemokine (C-C motif), receptor2 nationallicence CD14 : Cluster of differentiation 14 nationallicence CHOP : C/EBP homologous protein nationallicence COX2 : Cyclooxygenase 2 nationallicence DC : Dendritic cells nationallicence DSS : Dextran sodium sulfate nationallicence ER : Endoplasmic reticulum nationallicence IBD : Inflammatory bowel disease nationallicence IL10 : Interleukin 10 nationallicence LPS : Lipopolysaccharide nationallicence MCP1 : Monocyte chemotactic protein-1 nationallicence NOD2 : Nucleotide-binding oligomerization domain containing 2 nationallicence PCNA : Proliferating cell nuclear antigen nationallicence PGE2 : prostaglandin E2 nationallicence PPARΎ : Peroxisome proliferator-activated receptor γ nationallicence P38MAPK : p38 mitogen-activated protein kinase nationallicence SLPi : Secretory leukoprotease inhibitor nationallicence Th1, 2 : T helper cell type 1, 2 nationallicence TLR : Toll-like receptor nationallicence TNFα : Tumor necrosis factor α nationallicence Arsenescu Violeta Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut Narasimhan Meena Plant Stress Genomics Research Center, King Abdullah University of Science and Technology, 23955-6900, Thuwal, Kingdom of Saudi Arabia aut Halide Tuna Microbiology, Immunology and Molecular Genetics, University of Kentucky, 40536, Lexington, KY, USA aut Bressan Ray Plant Stress Genomics Research Center, King Abdullah University of Science and Technology, 23955-6900, Thuwal, Kingdom of Saudi Arabia aut Barisione Chiara Research Center of Cardiovascular Biology, University of Genoa, 16126, Liguria, Italy aut Cohen Donald Microbiology, Immunology and Molecular Genetics, University of Kentucky, 40536, Lexington, KY, USA aut de Villiers Willem Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut Arsenescu Razvan Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/10(2011-10-01), 2818-2832 0163-2116 56:10<2818 2011 56 10620 https://doi.org/10.1007/s10620-011-1692-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1692-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Arsenescu Violeta Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut NATIONALLICENCE 700 1- Narasimhan Meena Plant Stress Genomics Research Center, King Abdullah University of Science and Technology, 23955-6900, Thuwal, Kingdom of Saudi Arabia aut NATIONALLICENCE 700 1- Halide Tuna Microbiology, Immunology and Molecular Genetics, University of Kentucky, 40536, Lexington, KY, USA aut NATIONALLICENCE 700 1- Bressan Ray Plant Stress Genomics Research Center, King Abdullah University of Science and Technology, 23955-6900, Thuwal, Kingdom of Saudi Arabia aut NATIONALLICENCE 700 1- Barisione Chiara Research Center of Cardiovascular Biology, University of Genoa, 16126, Liguria, Italy aut NATIONALLICENCE 700 1- Cohen Donald Microbiology, Immunology and Molecular Genetics, University of Kentucky, 40536, Lexington, KY, USA aut NATIONALLICENCE 700 1- de Villiers Willem Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut NATIONALLICENCE 700 1- Arsenescu Razvan Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Room MN 649, 40536, Lexington, KY, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/10(2011-10-01), 2818-2832 0163-2116 56:10<2818 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer