title: Role of myosin light chain kinase in intestinal epithelial barrier defects in a rat model of bowel obstruction.
abstract: BACKGROUND
  Bowel obstruction is a common cause of abdominal emergency, since the patients are at increased risk of septicemia resulting in high mortality rate. While the compartmentalized changes in enteric microfloral population and augmentation of bacterial translocation (BT) have already been reported using experimental obstruction models, alterations in epithelial permeability of the obstructed guts has not been studied in detail. Myosin light chain kinase (MLCK) is actively involved in the contraction of epithelial perijunctional actinomyosin ring and thereby increases paracellular permeability. In the current study we attempt to investigate the role of MLCK in epithelial barrier defects using a rat model of simple mechanical obstruction.
  
  
  METHODS
  Wistar rats received intraperitoneal injection of ML-7 (a MLCK inhibitor) or vehicle at 24, 12 and 1 hrs before and 12 hrs after intestinal obstruction (IO). The distal small intestine was obstructed with a single ligature placed 10 cm proximal to the ileocecal junction in IO rats for 24 hrs. Sham-operated rats served as controls.
  
  
  RESULTS
  Mucosal injury, such as villous blunting and increased crypt/villus ratio, was observed in the distal small intestine of IO rats. Despite massive enterocyte shedding, intestinal villi were covered with a contiguous epithelial layer without cell apoptosis. Increased transmural macromolecular flux was noticed in the distal small intestine and the proximal colon after IO. The bacterial colony forming units in the spleen and liver of IO rats were significantly higher than those of sham controls. Addition of ML-7 ameliorated the IO-triggered epithelial MLC phosphorylation, mucosal injury and macromolecular flux, but not the level of BT.
  
  
  CONCLUSIONS
  The results suggest that IO-induced premature enterocytic sloughing and enhanced paracellular antigenic flux were mediated by epithelial MLCK activation. In addition, enteric bacteria may undergo transcytotic routes other than paracellular paths to cross the epithelium.
authors.affiliation: National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Chin
authors.initials: CC
authors.lastname: Wu
authors.forename: Yen-Zhen
authors.initials: YZ
authors.lastname: Lu
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Wu
authors.forename: Linda C
authors.initials: LC
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002463:Cell Membrane Permeability / Q000502:physiology*; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000378:metabolism*; D007415:Intestinal Obstruction / Q000201:enzymology* / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004247:DNA; D009219:Myosin-Light-Chain Kinase
references.citation: Surgery. 2005 Jan;137(1):85-91
references.pmid: 15614285
references.citation: Gastroenterology. 2005 Sep;129(3):902-12
references.pmid: 16143130
references.citation: J Infect Dis. 2006 Jan 15;193(2):241-50
references.pmid: 16362888
references.citation: Am J Pathol. 2006 Jan;168(1):104-14; quiz 363
references.pmid: 16400013
references.citation: Development. 1990 Dec;110(4):1001-20
references.pmid: 2100251
references.citation: J Trauma. 2008 Jun;64(6):1651-64
references.pmid: 18545135
references.citation: J Cell Sci. 2006 May 15;119(Pt 10):2095-106
references.pmid: 16638813
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11104-9
references.pmid: 12960392
references.citation: Curr Gastroenterol Rep. 2008 Oct;10(5):443-9
references.pmid: 18799118
references.citation: Gastroenterology. 2003 Sep;125(3):795-804
references.pmid: 12949725
references.citation: Curr Biol. 2001 Nov 27;11(23):1847-57
references.pmid: 11728307
references.citation: J Biol Chem. 2004 Dec 31;279(53):55506-13
references.pmid: 15507455
references.citation: Med Clin North Am. 2008 May;92(3):575-97, viii
references.pmid: 18387377
references.citation: J Immunol. 2003 Dec 1;171(11):6164-72
references.pmid: 14634132
references.citation: Lab Invest. 2006 Oct;86(10):1052-63
references.pmid: 16909128
references.citation: Int J Parasitol. 2008 Jul;38(8-9):923-34
references.pmid: 18281046
references.citation: World J Surg. 2007 Sep;31(9):1806-1812
references.pmid: 17610111
references.citation: Am J Pathol. 2005 Feb;166(2):409-19
references.pmid: 15681825
references.citation: J Parasitol. 1990 Jun;76(3):403-9
references.pmid: 2191103
references.citation: Am J Pathol. 2004 Mar;164(3):947-57
references.pmid: 14982848
references.citation: Gastroenterology. 1986 Sep;91(3):673-82
references.pmid: 2942438
references.citation: Infect Immun. 2004 Jun;72(6):3536-42
references.pmid: 15155662
references.citation: Shock. 2003 Apr;19(4):378-82
references.pmid: 12688551
references.citation: J Membr Biol. 1990 Jun;116(2):177-84
references.pmid: 2380981
references.citation: Dis Colon Rectum. 1995 Jun;38(6):640-4
references.pmid: 7774478
references.citation: Mol Biol Cell. 2005 Oct;16(10):5040-52
references.pmid: 16055505
references.citation: J Biol Chem. 2006 Sep 8;281(36):26205-15
references.pmid: 16835238
references.citation: Invest Radiol. 2009 Jun;44(6):329-35
references.pmid: 19363446
references.citation: FASEB J. 2005 Nov;19(13):1822-35
references.pmid: 16260652
references.citation: Gastroenterology. 2002 Oct;123(4):1179-90
references.pmid: 12360480
references.citation: Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G875-85
references.pmid: 11052983
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Jul;285(1):G223-34
references.pmid: 12637252
references.citation: Gastroenterology. 2002 Jul;123(1):163-72
references.pmid: 12105845
references.citation: Gastroenterology. 2000 Dec;119(6):1524-36
references.pmid: 11113074
references.citation: J Invest Surg. 2003 Jan-Feb;16(1):23-8
references.pmid: 12554336
references.citation: Am J Physiol. 1999 Sep;277(3):C554-62
references.pmid: 10484342
references.citation: Am J Surg. 1990 Apr;159(4):394-401
references.pmid: 2316803
references.citation: Arch Surg. 1970 Oct;101(4):478-83
references.pmid: 5457245
references.citation: Am J Physiol Cell Physiol. 2004 Mar;286(3):C693-707
references.pmid: 14644769
references.citation: Ann N Y Acad Sci. 2006 Aug;1072:276-87
references.pmid: 17057207
references.citation: Gastroenterology. 2005 May;128(5):1258-67
references.pmid: 15887109
references.citation: Am J Pathol. 2005 Oct;167(4):1071-9
references.pmid: 16192642
references.citation: Scand J Gastroenterol. 2008;43(9):1030-7
references.pmid: 18609165
references.citation: Ann Surg Oncol. 2001 Sep;8(8):632-7
references.pmid: 11569777
references.citation: BMC Surg. 2002 Aug 13;2:6
references.pmid: 12174194
references.citation: Shock. 2007 Oct;28(4):384-93
references.pmid: 17577136