Syndecan-4 Deficiency Leads to High Mortality of Lipopolysaccharide-injected Mice

Kazuhiro Ishiguro, Kenji Kadomatsu, Tetsuhito Kojima, Hisako Muramatsu, Mitsunori Iwase, Yasunobu Yoshikai, Masamitsu Yanada, Koji Yamamoto, Tadashi Matsushita, Masahiko Nishimura, Kazuo Kusugami, Hidehiko Saito, Takashi Muramatsu

    Research output: Contribution to journalArticlepeer-review

    100 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)47483-47488
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume276
    Issue number50
    DOIs
    Publication statusPublished - Dec 14 2001

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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