Protective Role of Rho Guanosine Diphosphate Dissociation Inhibitor, Ly-GDI, in Pulmonary Alveolitis

PLoS One. 2015 Oct 15;10(10):e0140804. doi: 10.1371/journal.pone.0140804. eCollection 2015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / genetics
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control
  • Animals
  • Cells, Cultured
  • Cytoprotection / genetics*
  • Genetic Therapy / methods
  • HEK293 Cells
  • Humans
  • Immunoglobulin G
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Pneumonia / genetics
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Pulmonary Alveoli / pathology*
  • rho Guanine Nucleotide Dissociation Inhibitor beta / genetics
  • rho Guanine Nucleotide Dissociation Inhibitor beta / physiology*


  • Arhgdib protein, mouse
  • Immunoglobulin G
  • Minor Histocompatibility Antigens
  • rho Guanine Nucleotide Dissociation Inhibitor beta