TY - JOUR
T1 - Syndecan-4 Deficiency Leads to High Mortality of Lipopolysaccharide-injected Mice
AU - Ishiguro, Kazuhiro
AU - Kadomatsu, Kenji
AU - Kojima, Tetsuhito
AU - Muramatsu, Hisako
AU - Iwase, Mitsunori
AU - Yoshikai, Yasunobu
AU - Yanada, Masamitsu
AU - Yamamoto, Koji
AU - Matsushita, Tadashi
AU - Nishimura, Masahiko
AU - Kusugami, Kazuo
AU - Saito, Hidehiko
AU - Muramatsu, Takashi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2001/12/14
Y1 - 2001/12/14
N2 - Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1β was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1β was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor-β1 was impaired in the syndecan-4-deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of transforming growth factor-β1 on IL-1β production.
AB - Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1β was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1β was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor-β1 was impaired in the syndecan-4-deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of transforming growth factor-β1 on IL-1β production.
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U2 - 10.1074/jbc.M106268200
DO - 10.1074/jbc.M106268200
M3 - Article
C2 - 11585825
AN - SCOPUS:0035861669
VL - 276
SP - 47483
EP - 47488
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 50
ER -