Homologous rat hepatic protease inhibitor genes show divergent functional responses to inflammation.
The genes encoding three distinct serine protease inhibitors (Spi) have been cloned from rat liver. These inhibitors are highly homologous with each other and are similar to alpha 1-antitrypsin at the nucleic and amino acid sequence level. Although previous investigators have examined the regulation of the Spi 2 locus by inflammation, the use of various techniques and the complexity of this genetic locus have led to incomplete and somewhat confusing results. Oligonucleotide probes specific for Spi 2.1, Spi 2.2, Spi 2.3, and a 3' mouse cDNA probe for alpha 1-antitrypsin mRNA were used to measure these mRNA after induction of inflammation with subcutaneous turpentine in Fischer rats. alpha 1-Antitrypsin mRNA increased 1.8-fold, and Spi 2.2 increased 7-fold. In contrast, Spi 2.1 and 2.3 mRNA sequences decreased fourfold. The maximal changes occurred between 24 and 48 h after inflammation, with a gradual return toward normal over the next 4 days. Since Spi 2.1, Spi 2.3, and alpha 1-antitrypsin mRNA sequences are responsive to growth hormone, two other growth hormone-responsive mRNA sequences, alpha 2u-globulin and insulin-like growth factor I, were measured, and they also decreased after induction of inflammation. The results of this study show that, despite a marked similarity of nucleotide sequence, Spi 2.1 and 2.3 genes respond very differently from Spi 2.2 and alpha 1-antitrypsin to both growth hormone and inflammation. We speculate that the functions of Spi 2.1 and 2.3 products are different from those of Spi 2.2 and alpha 1-antitrypsin and may involve the regulation of growth.
Department of Biochemistry, University of Minnesota, Minneapolis 55455.
S J
SJ
Schwarzenberg
J B
JB
Yoon
H L
HL
Sharp
S
S
Seelig
D000818:Animals; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D005796:Genes; D013006:Growth Hormone / Q000097:blood; D007249:Inflammation; D008099:Liver / Q000503:physiopathology*; D008297:Male; D011480:Protease Inhibitors / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012689:Sequence Homology, Nucleic Acid; D015842:Serine Proteinase Inhibitors; D014158:Transcription, Genetic; D014425:Turpentine
D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D013006:Growth Hormone; D014425:Turpentine