DNA clones representing the negative acute-phase gene coding for the plasma
proteinase inhibitor
alpha 1-inhibitor III were isolated from a rat genomic library. Structural analysis established the existence of at least four different members of the
alpha 1-inhibitor III gene family. Partial DNA sequence analysis of the 5'-terminal regions was performed for the
alpha 1-inhibitor III gene and the related alpha 1-inhibitor IV gene. The transcription start site of the
alpha 1-inhibitor III gene was located by S1 mapping and primer extension. No stable alpha 1-inhibitor IV
mRNA was detected in rat liver. In an experimentally induced
acute-phase reaction, the transcription rate of the
alpha 1-inhibitor III gene was reduced 12.7-fold at 6 h after stimulation. Four hours after injection of a high dose of
dexamethasone into rats, the transcription rate of this gene was reduced 9-fold. Thus,
glucocorticoids alone are capable of causing a strong transient down-regulation of the transcription of this gene in rats, independent of other inflammatory mediators. An inverted consensus
glucocorticoid responsive
element (5'GGACACAATAT3') shared with the
glucocorticoid-regulated alpha 1-fetoprotein, alpha 2u-globulin, and
alpha 1-acid glycoprotein genes was detected by computer-assisted sequence analysis in the promoter proximal 5'-flanking region of the
alpha 1-inhibitor III gene.