Research Project
Grant-in-Aid for Scientific Research (A)
In this study, we investigated the nature and function of both host-and bacteria-derived proteases in host immune system. Cathepsin E (catE) and gingipains were treated as a host-derived endolysosomal protease and bacterial proteases, respectively. The obtained results are as follows : (i) CatE differentially regulated the nature and function of dendritic cells and macrophages, (ii) CatE deficiency caused impairment of autophagy in macrophages manifesting mitochondria dysfunction and enhanced oxidative stress, (iii) Endogenous Cat E expression levels were positively associated with the growth arrest and metastasis reduction of tumor cells in vivo and the concomitant increase of tumor-associated activated macrophages in tumor microenvironment, (iv) CatE specifically induced apoptosis in tumor cells without affecting normal cells in vitro by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface, (v) Peptide-aptamer-based inhibitors and activators of CatE was generated by cDNA display techniques, (vi) Atherosclerosis progression in apolipoprotein E-knockout mice was accelerated by P. gingivalis infection, which was mediated by selective proteolysis of apolipoprotein B-100 by Arg-gingipain (Rgp), (vii) A risk for preterm birth and fetal death in pregnant mice was enhanced by P. gingivalis infection and inhibited by combination treatment of Rgp and Kgp inhibitors, (iii) A newly developed peptide analogue inhibiting both Rgp and Kgp suppressed most of the pethogenicity of P. gingivalis.
All 2010 2009 2008 2007
All Journal Article (34 results) (of which Peer Reviewed: 34 results) Presentation (41 results) Patent(Industrial Property Rights) (4 results)
Biol Chem (in press)
120006900038
Biol Chem (In press)
J. Biochem. 145(5)
Pages: 565-573
J. Mol. Biol. 387
Pages: 1186-1198
J. Biochem. 145
Journal of Molecular Biology 387
Journal of Biochemistry 145(In press)
J. Neurochem. 105
Pages: 1394-1404
Arch. Oral Biol. 53(6)
Pages: 538-544
120006984583
Brain Res. 1198
Pages: 55-67
Biochimie 90
Pages: 396-404
120006900027
Journal of Neurochemistry 105
Archives Oral Biology 53
Brain Research 1198
Surface. Cancer Res. 67
Pages: 10869-10878
J. Immunol. 179
Pages: 5728-5737
FEBS Lett. 581
Pages: 4260-4264
J. Bacteriol. 189
Pages: 3977-3986
J. Biol. Chem. 282
Pages: 1851-1862
Biol. Chem. 388
Pages: 1173-1181
120006900037
Frontiers in Biosci. 12
Pages: 4800-4809
Infect. Immun. 75
Pages: 2090-2100
J. Mol. Recognit. 20
Pages: 58-68
The Journal of Immunology 179
Cancer Research 67
FEBS Letter 581
Journal Bacteriology 189
Biological Chemistry 388
Frontiers in Bioscience 12
Infection and Immunity 75
Journal Molecular Recognition 20
Journal of Biological Chemistry 282