Upregulation of geranylgeranyltransferase I in bronchial smooth muscle of mouse experimental asthma: its inhibition by lovastatin.

RhoA has been recognized as an important protein for bronchial smooth muscle (BSM) contraction and hyperresponsiveness, and its activation is also regulated by geranylgeranyltransferase I (GGTase I). In the present study, the effects of repeated antigen exposure on the expression of GGTase I were determined in mouse BSMs. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. Animals were also treated with lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen inhalation period. Western blot analyses revealed that GGTase I was upregulated in BSMs of the antigen-challenged mice. The systemic treatment with lovastatin attenuated the upregulation of GGTase I induced by antigen exposure. Interestingly, lovastatin also significantly reduced the protein expression of GGTase I in BSMs of control animals. We thus concluded that an upregulation of GGTase I in BSM might be, at least in part, involved in the development of antigen-induced airway hyperresponsiveness. Lovastatin might have therapeutic potential to ameliorate airway hyperresponsiveness in allergic bronchial asthma.