Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

GGTI-2133, an inhibitor of geranylgeranyltransferase, inhibits infiltration of inflammatory cells into airways in mouse experimental asthma.

Authors: Chiba, Y  Sato, S  Misawa, M 
Citation: Chiba Y, etal., Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):929-35.
Pubmed: (View Article at PubMed) PMID:20074456

Statins have been proposed as a novel treatment of respiratory diseases including asthma. Although the mechanism of anti-inflammatory effect of statins is still unclear, an inhibition of protein prenylation by depleting the downstream metabolites of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase might be involved. To test the hypothesis, the effects of GGTI-2133, a direct inhibitor of geran ylgeranyltransferase (GGTase), on antigen-induced airway inflammation were investigated in a murine model of allergic bronchial asthma. Mice were sensitized and repeatedly challenged with ovalbumin antigen (OA). Animals were also treated with GGTI-2133 (5 mg/kg/day, i.p.) once a day before and during the antigen inhalation period. Repeated antigen inhalation caused an infiltration of inflammatory cells, especially eosinophils, into airways. Significant increases in interleukin (IL)-4, IL-13, eotaxin, thymus and activation-regulated chemokine (TARC) and leukotriene B4 (LTB4) in bronchoalveolar lavage fluids and total and OA-specific IgE in sera were also found in the antigen-exposed animals. The systemic treatments with GGTI-2133 inhibited the antigen-induced eosinophil infiltration into airways almost completely. However, interestingly, the GGTI-2133 treatment did not affect the levels of these chemotactic factors and IgE. These findings suggest that selective inhibition of GGTase is effective for eosinophilic airway inflammation such as asthma.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 4145487
Created: 2010-11-05
Species: All species
Last Modified: 2010-11-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.