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Pancreatic secretory trypsin inhibitor reduces multi-organ injury caused by gut ischemia/reperfusion in mice


Autoři: Raymond J. Playford aff001;  Tania Marchbank aff002
Působiště autorů: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom aff001;  Centre of Immunobiology, Blizard Institute, Barts and The London School of Medicine, Queen Mary, University of London, London, United Kingdom aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227059

Souhrn

Intestinal ischemia/reperfusion (I/R) injury occurs during transplantation, mesenteric arterial occlusion, trauma and shock, causing systemic inflammation, multiple organ dysfunction and high mortality. Pancreatic secretory trypsin inhibitor (PSTI), a serine protease inhibitor expressed in gut mucosa may function as a mucosal protective/repair peptide. We examined whether PSTI affected mesenteric I/R-induced injury. Hypoxia/normoxia (H/N) caused 50% drop in cell viability of AGS, RIE1 and Caco-2 cells but PSTI (10 μg/ml) given prior- or during-hypoxic period improved survival by 50% (p<0.01). Similarly, Caco-2 monolayers exposed to H/N had 300% increase in transepithelial permeability, PSTI truncated this by 50% (p<0.01). Mice underwent mesenteric I/R by clamping jejunum, causing severe mucosal injury, increased apoptotic markers and 3-fold increases in plasma IL-6, IL1β, TNFα, and tissue lipid peroxidation (MDA) and inflammatory infiltration (MPO) levels. Lungs showed similar significant injury and inflammatory infiltrate markers. Smaller increases in MDA and MPO were seen in kidney & liver. PSTI (20 mg/kg) reduced all injury markers by 50–80% (p<0.01). In vitro and in vivo studies showed PSTI reduced pro-apoptotic Caspase 3, 9 and Baxα levels, normalised Bcl2 and caused additional increases in HIF1α, VEGF and Hsp70 above rises caused by I/R alone (all p<0.01). PSTI also prevented reduction of tight junction molecules ZO1 and Claudin1 (all p<0.01) but did not affect increased ICAM-1 caused by I/R in gut or lung. PSTI may be a useful clinical target to prevent I/R injury.

Klíčová slova:

Apoptosis – Gastrointestinal tract – Histology – Hypoxia – Kidneys – MTT assay – Permeability – Reperfusion


Zdroje

1. Nankervis CA, Giannone PJ, Reber KM. The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin Perinatol 2008; 32:83–91. doi: 10.1053/j.semperi.2008.01.003 18346531

2. Corcos O, Nuzzo A. Gastro-intestinal vascular emergencies. Best Pract Res Clin Gastroenterol 2013; 27:709–725. doi: 10.1016/j.bpg.2013.08.006 24160929

3. Sastry P, Hardman G, Page A, Parker R, Goddard M, Large S, Jenkins DP. Mesenteric ischaemia following cardiac surgery: the influence of intraoperative perfusion parameters. Interact Cardiovasc Thorac Surg 2014; 19:419–424. doi: 10.1093/icvts/ivu139 24939960

4. Fishman JE, Sheth SU, Levy G, Alli V, Lu Q, Xu D, Qin Y, Qin X, Deitch EA. Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock. Ann Surg 2014; 260: 1112–1120. doi: 10.1097/SLA.0000000000000631 24646554

5. Moore EE, Moore FA, Franciose RJ, Kim FJ, Biffl WL, Banerjee A. The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma. 1994; 37:881–7. doi: 10.1097/00005373-199412000-00002 7996599

6. Hassoun HT, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock. 2001; 15:1–10.

7. Eltzschig HK, Bratton DL, Colgan SP. Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases. Nat Rev Drug Discov. 2014; 13:852–69. doi: 10.1038/nrd4422 25359381

8. Klingensmith NJ, Coopersmith CM. The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness. Crit Care Clin. 2016; 32:203–12. doi: 10.1016/j.ccc.2015.11.004 27016162

9. Kazal LA, Spicer DS, Brahinsky RA. Isolation of a crystalline trypsin inhibitor-anticoagulant protein from the pancreas. J Am Chem Soc. 1948; 70:304–340.

10. Marchbank T, Chinery R, Hanby AM, Poulsom R, Elia G, Playford RJ. Distribution and expression of pancreatic secretory trypsin inhibitor and its possible role in epithelial restitution. Am J Pathol. 1996; 148:715–722. 8774127

11. Playford RJ, Hanby AM, Patel K, Beardshall K, Poulter L, Young J, Calam J. Influence of inflammatory bowel disease on the distribution and concentration of pancreatic secretory trypsin inhibitor within the colon. Am J Pathol. 1995; 146:310–316. 7856742

12. Marchbank T, Mahmood A, Fitzgerald AJ, Domin J, Butler M, Goodlad RA, et al. Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents. Am J Pathol. 2007; 171:1462–73. doi: 10.2353/ajpath.2007.070192 17982125

13. Marchbank T, Mahmood A, Playford RJ. Pancreatic secretory trypsin inhibitor causes autocrine-mediated migration and invasion in bladder cancer and phosphorylates the EGF receptor, Akt2 and Akt3, and ERK1 and ERK2. Am J Physiol Renal Physiol. 2013; 305:F382–9. doi: 10.1152/ajprenal.00357.2012 23698120

14. Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 1977; 59:221–6. doi: 10.1093/jnci/59.1.221 327080

15. Barranco SC, Townsend CM Jr, Casartelli C. Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res. 1983, 43:1703–1709 6831414

16. Blay J, Brown KD. Characterization of an epithelioid cell line derived from rat small intestine: demonstration of cytokeratin filaments. Cell Biol Int Rep. 1984; 8:551–60. doi: 10.1016/0309-1651(84)90054-7 6204784

17. Marshall NJ, Goodwin CJ, Holt SJ. A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. Growth Regul. 1995; 5:69–84. 7627094

18. Davison G, Marchbank T, March DS, Thatcher R, Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016; 104:526–36. doi: 10.3945/ajcn.116.134403 27357095

19. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101:478. doi: 10.1001/archsurg.1970.01340280030009 5457245

20. Koksel O, Yildirim C, Cinel L, Tamer L, Ozdulger A, Bastürk M, et al. Inhibition of poly (ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia reperfusion in rats. Pharmacol Res 2005; 51:453–462. doi: 10.1016/j.phrs.2004.11.007 15749460

21. FitzGerald AJ, Pu M, Marchbank T, Westley BR, May FE, Boyle J, et al. Synergistic effects of systemic trefoil factor family 1 (TFF1) peptide and epidermal growth factor in a rat model of colitis. Peptides. 2004; 25:793–801. doi: 10.1016/j.peptides.2003.12.022 15177874

22. Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta. 1978; 90:37–43. doi: 10.1016/0009-8981(78)90081-5 719890

23. Gonzalez LM, Moeser AJ, Blikslager AT. Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research. Am J Physiol Gastrointest Liver Physiol. 2014; 308:G63–75. doi: 10.1152/ajpgi.00112.2013 25414098

24. Berlanga J, Prats P, Remirez D, Gonzalez R, Lopez-Saura P, Aguiar J, et al. Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage. Am J Pathol. 2002; 161:373–9. doi: 10.1016/S0002-9440(10)64192-2 12163361

25. Moore EE. Splanchnic hypoperfusion provokes acute lung injury via a 5-lipoxygenase-dependent mechanism. Am J Surg. 2010; 200:681–9. doi: 10.1016/j.amjsurg.2010.05.010 21146002

26. Moraes LB, Murakami AH, Fontes B, Poggetti RS, van Rooijen N, Younes RN, et al. Gut ischemia/reperfusion induced acute lung injury is an alveolar macrophage dependent event. J Trauma. 2008; 64:1196–2000. doi: 10.1097/TA.0b013e31816c5ca6 18469641

27. Rokutan K. Role of heat shock proteins in gastric mucosal protection. J Gastroenterol Hepatol 2000; 15:D12–9. doi: 10.1046/j.1440-1746.2000.02144.x 10759215

28. Karhausen J1, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004; 114:1098–106. doi: 10.1172/JCI21086 15489957

29. Cummins EP, Keogh CE, Crean D, Taylor CT. The role of HIF in immunity and inflammation. Mol Aspects Med. 2016; 47–48:24–34. doi: 10.1016/j.mam.2015.12.004 26768963

30. Zhao H, Montalto MC, Pfeiffer KJ, Hao L, Stahl G. Murine model of gastrointestinal ischemia associated with complement-dependent injury. J Appl Physiol 1985; 93:338–45.

31. Niinobu T, Ogawa M, Murata A, Nishijima J, Mori T. Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor. J Exp Med 1990; 172:1133–1142 doi: 10.1084/jem.172.4.1133 2170560

32. Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W. Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J 392: 249–261, 2005. doi: 10.1042/BJ20050908 16293107

33. Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life 2006; 58: 621–31. doi: 10.1080/15216540600957438 17085381

34. Sheng H, Shao J, Townsend CM Jr, Evers BM. Phosphatidylinositol 3-kinase mediates proliferative signals in intestinal epithelial cells. Gut 2003; 52:1472–8. doi: 10.1136/gut.52.10.1472 12970141

35. Dillon RL, Muller WJ. Distinct biological roles for the akt family in mammary tumor progression. Cancer Res 2010; 70:4260–4. doi: 10.1158/0008-5472.CAN-10-0266 20424120

36. Marchbank T, Freeman TC, Playford RJ. Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible role in mucosal integrity and repair. Digestion. 1998; 59:167–74. doi: 10.1159/000007485 9643675

37. Kikuchi K, Kurokawa H, Matsumoto F, Iwashita S, Miyagi F, Nagai K, et al. Responses of cytokines, acute phase proteins, and polymorphonuclear cell elastase to surgical stress in the patients with esophageal cancer. Rinsho Byori. 1996; 44:579–84. 8752738


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