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Originally published In Press as doi:10.1074/jbc.M108382200 on November 21, 2001
J. Biol. Chem., Vol. 277, Issue 7, 4816-4822, February 15, 2002
Involvement of Cathepsin E in Exogenous Antigen Processing in
Primary Cultured Murine Microglia*
Tsuyoshi
Nishioku §,
Koichi
Hashimoto¶,
Keizo
Yamashita¶,
Shyh-Yuh
Liou¶,
Yoshifumi
Kagamiishi ,
Hitoshi
Maegawa ,
Nobuo
Katsube ,
Christoph
Peters**,
Kurt
von Figura ,
Paul
Saftig ,
Nobuhiko
Katunuma§§,
Kenji
Yamamoto , and
Hiroshi
Nakanishi§¶¶
From the Department of Pharmacology, Graduate School
of Dental Science and § Laboratory of Oral Aging Science,
Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan,
the ¶ Tsukuba Research Laboratories, Nippon Glaxo Ltd., Tsukuba
300-4247, Japan, the Minase Research Institute, Ono
Pharmaceutical Co., Ltd., Osaka 618-8585, Japan, the
** Institute für Molekulare Medizin und Zellforschung,
Albert-Ludwings-Universität Freiburg Hugstetter Strasse 55, 79106 Freiburg, Germany, the  Center for Biochemistry and
Molecular Cell Biology, Göttingen University,
Heinrich-Düker Weg 12, 37037 Göttingen, Germany, and the
§§ Tokushima Bunri University, Institute for Health
Sciences, Tokushima 770-8514, Japan
We have attempted to elucidate an involvement of
cathepsin E (CE) in major histocompatibility complex class II-mediated
antigen presentation by microglia. In primary cultured murine
microglia, CE was localized mainly in early endosomes and its
expression level was markedly increased upon stimulation with
interferon- . Pepstatin A, a specific inhibitor of aspartic
proteases, significantly inhibited interleukin-2 production from an
OVA-(266-281)-specific T helper cell hybridomas upon
stimulation with native OVA presented by interferon- -treated
microglia. However, pepstatin A failed to inhibit the presentation of
OVA-(266-281) peptide. The possible involvement of CE in the
processing of native OVA into antigenic peptide was further
substantiated by that digested fragments of native OVA by CE could be
recognized by OVA-specific Th cells. Cathepsin D also degraded native
OVA into antigenic peptide, whereas microglia prepared from cathepsin
D-deficient mice retained an ability for antigen presentation. On the
other hand, the requirement for cysteine proteases such as cathepsins S
and B in the processing of invariant chain (Ii) was confirmed by
immunoblot analyses in the presence of their specific inhibitors. In
conclusion, CE is required for the generation of an antigenic epitope
from OVA but not for the processing of Ii in microglia.
*
This work was supported in part by a grant-in-aid for
Scientific Research from the Ministry of Education, Science, and
Culture of Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶¶
To whom all correspondence should be addressed:
Laboratory of Oral Aging Science, Faculty of Dental Science, Kyushu
University, Fukuoka 812-8582, Japan. Tel.: 81-92-642-6413; Fax:
81-92-642-6283; E-mail: nakandeg@mbox.nc.kyushu-u.ac.jp.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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