Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes,
ORM1 and
ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each
ORM in HeLa cells. Luciferase-reporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of
ORM1 and
ORM2 were compared under both basal and inducer-treated conditions. For
ORM1 and
ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for
ORM1 after IL-1β treatment, while those for
ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for
ORM1, and at basal level and after inducer-treatments for
ORM2. Higher transcription-induction activity in the distal promoter region was evident for
ORM1 in the absence of C/EBPβ overexpression, and for
ORM2 under C/EBPβ overexpression conditions. These findings suggest that the
ORM distal promoter region differentially regulates expression of
ORM genes at basal level and in acute phase responses.
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