Tripeptide feG Prevents and Ameliorates Acute Pancreatitis-Associated Acute Lung Injury in a Rodent Model

Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif

“…Unfortunately we do not currently know the mechanism of action of our peptides, so we are unable to determine whether the differences between the two assays are due to species variation, differential binding affinities of the peptides to their targets in these models, or lower sensitivity and greater variability of the intestinal anaphylaxis model. There is evidence that neutrophils are involved either directly or downstream from the action of the anti-inflammatory peptides from rat SMR1 (2,11,18,20), and this could help explain why the human peptides have greater efficacy in the LPS-induced neutrophilia model in the mouse than in an anaphylactic assay, which has, at least until recently (13), been thought to have little or no neutrophil involvement. We have also observed differences with various peptide sequences from rat SMR1 in their activities in distinct inflammatory models (19,22,31).…”

“…SMR1 is a prohormone and contains the amino acid (aa) sequence TDIFEGG near the COOH-terminus. This peptide and a modified sequence feG (Phe-Glu-Gly) have anti-inflammatory and antishock properties (16,17), and feG has been shown in many animal models to reduce inflammation and improve outcomes in preclinical models of spinal cord injury (2,12), allergic asthma (6,8,9), lung injury (10,11), and acute pancreatitis (3,25). Another sequence, QHNPR (sialorphin), near the NH 2 terminus of SMR1, has analgesic activity (28) and regulates sexual behavior and erectile function in rats (5,21).…”

Prevention and Amelioration of Rodent Ventilation-Induced Lung Injury with Either Prophylactic or Therapeutic feG Administration

“…Dose-response assays have demonstrated a bell-shaped response curve, with neither lower (10 μg/kg) or higher (350 μg/kg) peptide doses inhibiting neutrophil migration in various models of injury [7]. Utilizing models of acute pancreatitis-associated lung injury we have demonstrated both prevention and amelioration of lung injury following prophylactic or therapeutic feG administration [8,10,11]. However, the ability of feG to similarly prevent or ameliorate mechanically induced lung damage such as in VILI has not been previously investigated.…”

“…The ability of a novel therapeutic pharmacological agent, the synthetic tripeptide feG ((D-Phe)-(D-Glu)-Gly), to decrease neutrophil recruitment, infiltration, and activation in vitro and in vivo has previously been demonstrated [7]. Possible mechanisms include decrease in integrin and adhesion molecule expression, and direct anti-inflammatory responses including decrease in reactive oxygen species and inflammatory cytokine production on neutrophils [7][8][9]. Dose-response assays have demonstrated a bell-shaped response curve, with neither lower (10 μg/kg) or higher (350 μg/kg) peptide doses inhibiting neutrophil migration in various models of injury [7].…”

Prevention and amelioration of rodent endotoxin-induced lung injury with administration of a novel therapeutic tripeptide feG

“…In vitro experiments previously suggested that feG requires pre-stimulation (such as with platelet-activating factorstimulation, ovalbumin or carrageenan) in order to decrease neutrophil chemotaxis in both humans and rat cell culture models [8]. In vivo we have similarly shown that inflammation and tissue damage in injured lung and pancreas tissue is significantly reduced, and respiratory function is improved, in mouse and rat models of acute pancreatitis-associated lung injury where feG is administered prior to lung injury (prophylactically) or after the initiation of lung injury (therapeutically), but following the potential pre-stimulation of pancreatic injury in both incidences [4,6]. However, the ability of feG to similarly prevent or ameliorate inflammatory damage in the lung without pre-stimulation has not been previously investigated.…”