Expression of protein S in the murine heart and cultured mouse cardiomyocytes is down-regulated by cytokines

Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependen t anticoagulant protein and is known to be produced extrahepatically, In th e present study, the concentration of PS mRNA was determined tissue by tiss ue in the mouse, and it was high in lung, adrenal and heart as well as in l iver. We further investigated the effects of lipopolysaccharide (LPS), tumo r necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1) on the PS mRN A expression in murine tissues in vivo. Although LPS and TNF-alpha signific antly decreased the expression level of PS mRNA in all tissues examined (e. g., lung, liver, heart, and kidney) and the PS anti-alpha level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were express ed in a cultured mouse cardiomyocyte cell line, and again, treatment with I L-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regiona l anticoagulant potential in heart, and suggest that the decreased PS expre ssion by cytokines may result in an increase in the systemic and/or regiona l prothrombotic potential under inflammatory conditions.