2009 Fiscal Year Final Research Report
The development of anti-tuberculosis gene drug inducing autophagy and activation of macrophages
| Project/Area Number |
20790145
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
FUJIWARA Naruyoshi Tokyo University of Science, 薬学部, 助教 (50365425)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 医療薬剤学 |
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| Research Abstract |
Tuberculosis, which is caused by Mycobacterium tuberculosis (MTB), is one of the most frequently occurring infections in the world. MTB is an intracellular parasitic bacterium that mainly infects the respiratory tract and hides in alveolar macrophages (AMs). Recently, it was reported that induction of autophagy in macrophages eliminates MTB1). In this study, we tried to develop a gene drug for inducing autophagy and activating macrophages. The genes, which related to atophagy and macrophage activation were first cloned by PCR and recombined into the expression vector (CAT7 neo). Each gene was then transfected to mouse macrophage cell line, RAW267.4 by using an Amaxa system. After introducing genes, the effects of these gene drug candidates were examined. The induction of autophagy in macrophages and activation of macrophages by some of our gene drugs were confirmed by fluorescent microscopic observation and western blot analysis. Based on these findings, it was shown that the gene drugs were effective for MTB. At present, the side effects such as inflammation by introducing gene drugs into macrophages are being estimated and the other candidates for gene drugs which induce autophagy and activation of macrophages are being screened.
1) Gutierrez, M.G.. et al. (2004). Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macro- phages. Cell 119, 753-766.
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