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

Elder, Alison S.F.; Bersten, Andrew D.; Saccone, Gino T.P.; Dixon, Dani‐Louise

doi:10.1016/j.pupt.2012.09.008

Cited by 4 publications

(8 citation statements)

References 32 publications

(40 reference statements)

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“…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).…”

mentioning

confidence: 99%

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

Laurent

Mathison

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.

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mentioning

confidence: 99%

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

Laurent

Mathison

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In addition, a 'two-hit' presentation of secondary bacterial infection on a background of VILI, modelled in this study through the intratracheal instillation of LPS, similarly resulted in amelioration and resolution of lung injury, following prophylactic or therapeutic feG administration. We previously established the efficacy of feG in inhibiting the inflammatory response and ameliorating and preventing injury in classically inflammatory models of acute lung injury [8,11]. Amelioration of lung injury in VILI, which is primarily a mechanically induced lung injury model, albeit with recognised inflammatory components [3], provides valuable additional insights into the mechanisms of action of feG.…”

Section: Discussionmentioning

confidence: 99%

“…A tracheotomy was performed before intratracheal instillation of lipopolysaccharide (LPS) (Escherichia coli O55:B5, 2 mg/kg body weight in saline; Sigma-Aldrich, MO) [6,11]. VILI was then induced by 2 h of injurious ventilation, as previously.…”

Section: Vili + Lpsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Elder

Bersten

Saccone

et al. 2019

Lung

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Purpose Mechanical ventilation is a well-established therapy for patients with acute respiratory failure. However, up to 35% of mortality in acute respiratory distress syndrome may be attributed to ventilation-induced lung injury (VILI). We previously demonstrated the efficacy of the synthetic tripeptide feG for preventing and ameliorating acute pancreatitis-associated lung injury. However, as the mechanisms of induction of injury during mechanical ventilation may differ, we aimed to investigate the effect of feG in a rodent model of VILI, with or without secondary challenge, as a preventative treatment when administered before injury (prophylactic), or as a therapeutic treatment administered following initiation of injury (therapeutic). Methods Lung injury was assessed following prophylactic or therapeutic intratracheal feG administration in a rodent model of ventilation-induced lung injury, with or without secondary intratracheal lipopolysaccharide challenge. Results Prophylactic feG administration resulted in significant improvements in arterial blood oxygenation and respiratory mechanics, and decreased lung oedema, bronchoalveolar lavage protein concentration, histological tissue injury scores, blood vessel activation, bronchoalveolar lavage cell infiltration and lung myeloperoxidase activity in VILI, both with and without lipopolysaccharide. Therapeutic feG administration similarly ameliorated the severity of tissue damage and encouraged the resolution of injury. feG associated decreases in endothelial adhesion molecules may indicate a mechanism for these effects. Conclusions This study supports the potential for feG as a pharmacological agent in the prevention or treatment of lung injury associated with mechanical ventilation.

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“…The tripeptide ImSAID Phe-Glu-Gly (FEG) attenuated both systemic [ 224 ] and pulmonary [ 225 , 226 ] inflammation. FEG significantly ameliorated endotoxin-induced lung injury in both a prophylactic and therapeutic manner in rats [ 227 ].…”

Section: Summary and Future Prospectsmentioning

confidence: 99%

Treatments for Pulmonary Ricin Intoxication: Current Aspects and Future Prospects

Gal

Mazor

Falach

et al. 2017

Toxins

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Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor beans), is one of the most lethal toxins known, particularly if inhaled. Ricin is considered a potential biological threat agent due to its high availability and ease of production. The clinical manifestation of pulmonary ricin intoxication in animal models is closely related to acute respiratory distress syndrome (ARDS), which involves pulmonary proinflammatory cytokine upregulation, massive neutrophil infiltration and severe edema. Currently, the only post-exposure measure that is effective against pulmonary ricinosis at clinically relevant time-points following intoxication in pre-clinical studies is passive immunization with anti-ricin neutralizing antibodies. The efficacy of this antitoxin treatment depends on antibody affinity and the time of treatment initiation within a limited therapeutic time window. Small-molecule compounds that interfere directly with the toxin or inhibit its intracellular trafficking may also be beneficial against ricinosis. Another approach relies on the co-administration of antitoxin antibodies with immunomodulatory drugs, thereby neutralizing the toxin while attenuating lung injury. Immunomodulators and other pharmacological-based treatment options should be tailored according to the particular pathogenesis pathways of pulmonary ricinosis. This review focuses on the current treatment options for pulmonary ricin intoxication using anti-ricin antibodies, disease-modifying countermeasures, anti-ricin small molecules and their various combinations.

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

Cited by 4 publications

References 32 publications

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

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

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

Treatments for Pulmonary Ricin Intoxication: Current Aspects and Future Prospects

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