Elevation of Circulating Monitor Peptide/Pancreatic Secretory Trypsin Inhibitor-I (PSTI-61) after Turpentine-Induced Inflammation in Rats: Hepatocytes Produce It as an Acute Phase Reactant

Abstract

Monitor peptide (MP) is a trypsin-sensitive cholecystokinin (CCK)-releasing peptide purified from rat pancreatic juice on the basis of its stimulatory activity toward pancreatic enzyme secretion and has been reported to exhibit cell growth-stimulating activity. Pancreatic secretory trypsin inhibitor (PSTI) prevents premature activation of trypsinogen in the pancreatic duct. There are two PSTIs (PSTI-61 and -56) purified from rat pancreatic juice on the basis of trypsin inhibitory activity as reported previously. Fushiki et al. (1989, FASEB J. 3, 121) showed that MP is structually the same peptide as PSTI-61. We measured the serial changes of circulating MP/PSTI-61 in rat and those in the level of PSTI-61 mRNA in the rat liver to investigate another novel role of this peptide in the turpentine-induced acute inflammation model. The elevation of serum MP/PSTI-61 as well as the α2-globulin fraction, which is known to include several acute phase reactants such as α2-macroglobulin and haptoglobin, was observed after induction of the turpentine inflammation. The serum α2-globulin fraction had increased approximately 3-fold over the initial level at 48 hr after the injection. In contrast, serum MP/PSTI-61 had increased approximately 17-fold over the initial level at 48 hr after the injection. The elevation of circulating MP/PSTI-61 was significantly related with that of the α2-globulin fraction (r = 0.91, P < 0.01). Immunoreactive MP/PSTI-61 was detected in the liver after induction of the inflammation (152.5 ± 16.5 ng/g wet weight), but in the normal rat liver there was no immunoreactive MP/PSTI-61. Furthermore, the elevated expression of PSTI-61 mRNA was only detected in the liver, using a synthetic oligonucleotide probe specific for PSTI-61. These results demonstrate that rat MP/ PSTI-61 is produced as an acute phase reactant in the liver in response to inflammatory stimuli, as well as other known acute phase reactants such as α2-macroglobulin and haptoglobin.