Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice.
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)-1beta 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-1beta 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-beta1 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-beta1 on IL-1beta production.
Ishiguro
K
K
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Kadomatsu
K
K
Kojima
T
T
Muramatsu
H
H
Iwase
M
M
Yoshikai
Y
Y
Yanada
M
M
Yamamoto
K
K
Matsushita
T
T
Nishimura
M
M
Kusugami
K
K
Saito
H
H
Muramatsu
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004727:Endothelium / Q000378:metabolism; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000172:deficiency*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012769:Shock / Q000401:mortality*; D053671:Syndecan-4; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D005982:Glutathione Transferase