title: Protective Role of Rho Guanosine Diphosphate Dissociation Inhibitor, Ly-GDI, in Pulmonary Alveolitis.
abstract: Growing evidences indicate that Ly-GDI, an inhibitory protein of Rho GTPases, plays an essential role in regulating actin cytoskeletal alteration which is indispensible for the process such as phagocytosis. However, the role of Ly-GDI in inflammation remains largely unknown. In the current study, we found that Ly-GDI expression was significantly decreased in the IgG immune complex-injured lungs. To determine if Ly-GDI might regulate the lung inflammatory response, we constructed adenovirus vectors that could mediate ectopic expression of Ly-GDI (Adeno-Ly-GDI). In vivo mouse lung expression of Ly-GDI resulted in a significant attenuation of IgG immune complex-induced lung injury, which was due to the decreased pulmonary permeability and lung inflammatory cells, especially neutrophil accumulation. Upon IgG immune complex deposition, mice with Ly-GDI over-expression in the lungs produced significant less inflammatory mediators (TNF-α, IL-6, MCP-1, and MIP-1α) in bronchoalveolar lavage fluid when compared control mice receiving airway injection of Adeno-GFP. Mechanically, IgG immune complex-induced NF-κB activity was markedly suppressed by Ly-GDI in both alveolar macrophages and lungs as measured by luciferase assay and electrophoretic mobility shift assay. These findings suggest that Ly-GDI is a critical regulator of inflammatory injury after deposition of IgG immune complexes and that it negatively regulates the lung NF-κB activity.
authors.affiliation: Department of Anesthesiology, Perioperative&Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Basic Sciences, University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Surgery, Tianjin Nankai Hospital, Tianjin, China.
authors.forename: Ximo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Perioperative&Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Raja-Elie
authors.initials: RE
authors.lastname: Abdulnour
authors.affiliation: Department of Basic Sciences, University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Perioperative&Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Surgery, Tianjin Nankai Hospital, Tianjin, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D011014:Pneumonia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000473:pathology*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000502:physiology*
chemical_list: C569659:Arhgdib protein, mouse; D007074:Immunoglobulin G; D015778:Minor Histocompatibility Antigens; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta