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* Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and
Solution-Oriented Research for Science and Technology of Japan Science and Technology Corp., Suita, Osaka, Japan
Macrophages produce a large amount of PGE2 during
inflammation. This lipid mediator modulates various immune responses.
PGE2 acts on macrophages and inhibits production of
cytokines such as TNF-
and IL-12. Membrane-bound
glutathione-dependent PGE2 synthase (mPGES) has been shown
to be a terminal enzyme of the cyclooxygenase-2-mediated
PGE2 biosynthesis. Here we identified mPGES as a molecule
that is induced by LPS in macrophages. The expression of mPGES was not
induced by LPS in mice lacking Toll-like receptor 4 or MyD88.
Furthermore, mice deficient in NF-IL6 showed neither induction of mPGES
nor biosynthesis of PGE2 in response to LPS, indicating
that mPGES expression in response to LPS is regulated by a Toll-like
receptor 4/MyD88/NF-IL6-dependent signaling pathway. We generated
mPGES-deficient mice and investigated the role of mPGES in vivo. The
mice showed no augmentation of the PGE2 production in
response to LPS. However, they were not impaired in the LPS-induced
production of inflammatory cytokines and showed normal response to the
LPS-induced shock. Thus, mPGES is critically involved in the
biosynthesis of PGE2 induced by LPS, but is dispensable for
the modulation of inflammatory responses.
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