start-ver=1.4
cd-journal=joma
no-vol=55
cd-vols=
no-issue=2
article-no=
start-page=105
end-page=115
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2001
dt-pub=200104
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Protection of mice from LPS-induced shock by CD14 antisense oligonucleotide.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>CD14 is a pattern recognition receptor on myeloid cells and plays a pivotal role in an innate immune system that is responsible for Gram-negative and Gram-positive bacteria infection. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, can induce production of a large quantity of proinflammatory cytokines into the circulation mediated by CD14-mediated macrophages and monocytes. These cytokines eventually cause septic shock. Several in vitro and in vivo studies have shown that suppression of a CD14 function by a CD14 antibody led to an inhibition of the production of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-8. In the present study, we found that CD14 antisense oligonucleotide (ODN) can prevent lethal LPS shock in D-galactosamine-sensitized mice. This ODN inhibited CD14 expression in a mouse macrophage cell line, RAW264.7, and suppressed production of TNF-alpha in LPS-stimulated RAW264.7 cells. Furthermore, we designed a consensus antisense ODN that could hybridize human and mouse CD14 RNA, and we evaluated its efficacy. The consensus antisense ODN rescued mice primed with Mycobacterium bovis bacillus Calmette-Guerin (BCG) from the LPS-induced lethal shock. In this model, the CD14 antisense ODN down-regulated LPS-elicited CD14 expression in the liver, resulting in a decrease in LPS-induced TNF-alpha production. These findings suggest that the CD14 antisense ODN is distributed in the liver and efficiently suppresses LPS-induced TNF-alpha production by reducing CD14 expression on Kupffer cells. This CD14 antisense ODN may be useful for the development of a therapeutic agent against sepsis and septic shock.</p>

en-copyright=
kn-copyright=

en-aut-name=FurusatoShoji
en-aut-sei=Furusato
en-aut-mei=Shoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakahashiTomohiro
en-aut-sei=Takahashi
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MoriSadao
en-aut-sei=Mori
en-aut-mei=Sadao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakahashiYasuo
en-aut-sei=Takahashi
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsudaToshihiko
en-aut-sei=Tsuda
en-aut-mei=Toshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NambaMasayoshi
en-aut-sei=Namba
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MochizukiHidenori
en-aut-sei=Mochizuki
en-aut-mei=Hidenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama University

affil-num=2
en-affil=
kn-affil=Okayama University

affil-num=3
en-affil=
kn-affil=Okayama University

affil-num=4
en-affil=
kn-affil=Okayama University

affil-num=5
en-affil=
kn-affil=Okayama University

affil-num=6
en-affil=
kn-affil=Okayama University

affil-num=7
en-affil=
kn-affil=Okayama University
en-keyword=sepsis
kn-keyword=sepsis
en-keyword=  TNF-?
kn-keyword=  TNF-?
en-keyword=  BCG(bacillus Calmette-Guerin)
kn-keyword=  BCG(bacillus Calmette-Guerin)
END