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Philip J O'Reilly, Qiang Ding, Samia Akthar, Guoqiang Cai, Kristopher R Genschmer, Dhiren F Patel, Patricia L Jackson, Liliana Viera, Mojtaba Roda, Morgan L Locy, Ellen A Bernstein, Clare M Lloyd, Kenneth E Bernstein, Robert J Snelgrove, J Edwin Blalock
The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE), and it is concomitantly degraded by extracellular leukotriene A4 hydrolase (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP, yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and can, thus, support a sustained neutrophilia. In this study, we sought to elucidate if an antiinflammatory system existed to degrade AcPGP that is analogous to the PGP-LTA4H axis...
November 16, 2017: JCI Insight
N S Bondarenko, A D Kurenkova, D A Nikishin, B A Umarova
Tripeptide glycyl-prolyl-proline (PGP), a regulatory peptide of the glyproline family, possesses a pronounced anti-inflammatory effect primarily due to its ability to prevent secretion of the proinflammatory mediator histamine by rat peritoneal mast cells. Activation of mast cell with synacthen (ACTH1-24) and substance 48/80 leads to an increase in intracellular calcium concentration. Pretreatment of mast cells with PGP prevented calcium entry into the cytoplasm from both intercellular space and intracellular stores...
August 2016: Bulletin of Experimental Biology and Medicine
Z V Bakaeva, A D Sangadzhieva, S Tani, N F Myasoedov, L A Andreeva, V I Torshin, J L Wallace, T Tanaka
Glyprolines have been reported to exert protective effects in the stomach. In this study, we examined the potential effects of intranasal administration of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on experimental gastric ulcer formation and healing. We also studied gastric release of the cytokine GRO/CINC-1, and its potential role in ulcer development and healing. Gastric ulcers were induced in rats by applying acetic acid to the serosa of the stomach. PGP and AcPGP were then administered at a dose of 3...
April 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
J Michael Wells, Patricia L Jackson, Liliana Viera, Surya P Bhatt, Joshua Gautney, Guy Handley, R Wilson King, Xin Xu, Amit Gaggar, William C Bailey, Mark T Dransfield, J Edwin Blalock
RATIONALE: Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) pathway is a novel means of neutrophilic inflammation that is pathologic in the development of COPD. AcPGP is produced by extracellular matrix collagen breakdown with prolyl endopeptidase and leukotriene A4 hydrolase serving as the enzymes responsible for its production and degradation, respectively...
October 15, 2015: American Journal of Respiratory and Critical Care Medicine
J Michael Wells, Philip J O'Reilly, Tomasz Szul, Daniel I Sullivan, Guy Handley, Chris Garrett, Carmel M McNicholas, Mojtaba Abdul Roda, Bruce E Miller, Ruth Tal-Singer, Amit Gaggar, Stephen I Rennard, Patricia L Jackson, J Edwin Blalock
RATIONALE: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated. OBJECTIVES: We investigated changes to the leukotriene A4 hydrolase (LTA4H)-proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD. METHODS: A/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis...
July 1, 2014: American Journal of Respiratory and Critical Care Medicine
Akio Shibata, Ichiro Morioka, Chitose Ashi, Shizu Nagasaki, Chisato Tode, Satoru Morikawa, Akihiro Miwa, Masahiro Enomoto, Kayoko Saiki, Naoki Yokoyama, Atsuko Takeuchi, Masafumi Matsuo
BACKGROUND: N-acetyl Proline-Glycine-Proline (acPGP) is a novel neutrophil chemoattractant. However, no studies have been reported to identify the presence of acPGP in human serum. The purpose of our study was to establish a method for measuring acPGP, and to determine whether acPGP is present in human serum. METHODS: Serum samples were obtained from 22 healthy adults and 26 term and preterm newborns. For the sensitive analysis of acPGP, we utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a multiple reaction monitoring (MRM) positive ion mode...
April 2009: Clinica Chimica Acta; International Journal of Clinical Chemistry
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