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Administration of nonviral gene vector encoding rat beta-defensin-2 ameliorates chronic Pseudomonas aeruginosa lung infection in rats.

AbstractBACKGROUND:
Beta-defensin-2 (BD-2) plays an important role in host defense against pathogenic microbe challenge by its direct antimicrobial activity and immunomodulatory functions. The present study aimed to determine whether genetic up-regulation of rat BD-2 (rBD-2) could ameliorate chronic Pseudomonas aeruginosa lung infection in rats.
METHODS:
Plasmid-encoding rBD-2 was delivered to lungs in vivo using linear polyethylenimine at 48 h before challenging with seaweed alginate beads containing P. aeruginosa. Macroscopic and histopathological changes of the lungs, bacterial loads, inflammatory infiltration, and the levels of cytokines/chemokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, kertinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2)] were measured at 3 and 7 days post-infection (p.i.).
RESULTS:
The overexpression of rBD-2 resulted in a significant increase in animal survival rate (at 3 days p.i.), a significant decrease in bacterial loads in the lungs (at 3 and 7 days p.i.), and significantly milder lung pathology. In addition, the overexpression of rBD-2 led to increased infiltration of polymorphonuclear neutrophils (PMN), and elevated protein expression of cytokines/chemokines (IL-1beta, TNF-alpha, KC and MIP-2) at the early stage of infection (at 3 days p.i.), at the same time as being dramatically decreased at the later stage of infection (at 7 days p.i.).
CONCLUSIONS:
Genetic up-regulation of rBD-2 increased animal survival rate, and reduced bacterial loads in lungs after bacterial infection. The overexpression of rBD-2 also modulated the production of several cytokines/chemokines and increased PMN recruitment at the early stage of infection. Our findings indicate that the enhancement of BD-2 may be an efficacious intervention for chronic P. aeruginosa lung infection.
AuthorsQiongjie Hu, Peng Zuo, Bing Shao, Shuo Yang, Guopeng Xu, Fen Lan, Xiaoxia Lu, Weining Xiong, Yongjian Xu, Shengdao Xiong
JournalThe journal of gene medicine (J Gene Med) Vol. 12 Issue 3 Pg. 276-86 (Mar 2010) ISSN: 1521-2254 [Electronic] England
PMID20131335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemokines
  • Cytokines
  • beta-Defensins
  • beta-defensin-2, rat
Topics
  • Animals
  • Chemokines (biosynthesis)
  • Chronic Disease
  • Cytokines (biosynthesis)
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy (methods)
  • Genetic Vectors (administration & dosage)
  • Pneumonia, Bacterial (immunology, pathology, therapy)
  • Pseudomonas Infections (immunology, pathology, therapy)
  • Pseudomonas aeruginosa
  • Rats
  • Rats, Sprague-Dawley
  • beta-Defensins (genetics)

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