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Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats.
- Source :
-
The American journal of pathology [Am J Pathol] 2005 Oct; Vol. 167 (4), pp. 1071-9. - Publication Year :
- 2005
-
Abstract
- Sepsis is associated with bacterial translocation (BT) and changes in colonic paracellular permeability (CPP), but the link between these effects is unknown. The present study aimed to identify whether changes in CPP after lipopolysaccharide (LPS) administration triggers BT, colonic inflammation, visceral pain, and sickness behavior and to evaluate the role of myosin light chain kinase (MLCK) in colonocyte cytoskeleton contraction. Rats received the MLCK inhibitor ML-7 alone or combined with LPS. CPP was measured for 6 hours after administration. Visceral pain, food intake, BT, electron microscopy of tight junctions of colonocytes, cytokine levels, and Western blotting of phosphorylated MLC from colonic mucosa were assessed in a time range of 0 to 3 hours after treatment. Sepsis increased CPP at 0 to 6 hours after LPS and associated with tight junction morphological changes, increased MLC phosphorylation, and mucosal release of proinflammatory cytokines. Massive BT, visceral hyperalgesia, and reduced food intake were also observed. Addition of ML-7 prevented all LPS-induced effects, except for changes in food intake. In conclusion, LPS-mediated effects on CPP include gut inflammation, BT, and visceral hyperalgesia. Inhibition of MLCK-dependent colonocyte cytoskeleton contraction by ML-7 prevents the LPS-induced alterations of CPP and its subsequent effects.
- Subjects :
- Animals
Azepines pharmacology
Blotting, Western
Cell Membrane Permeability drug effects
Colon cytology
Colon ultrastructure
Diarrhea chemically induced
Eating drug effects
Electromyography
Enzyme Inhibitors pharmacology
Inflammation etiology
Inflammation pathology
Injections, Intraperitoneal
Interferon-gamma analysis
Interferon-gamma metabolism
Interleukin-1 analysis
Interleukin-1 metabolism
Interleukin-6 analysis
Interleukin-6 metabolism
Intestinal Mucosa enzymology
Intestinal Mucosa pathology
Intestinal Mucosa ultrastructure
Kinetics
Lipopolysaccharides administration & dosage
Male
Muscle Contraction
Muscle, Skeletal physiology
Naphthalenes pharmacology
Pain Measurement
Phosphorylation
Proteins analysis
Proteins metabolism
Rats
Rats, Wistar
Tight Junctions ultrastructure
Tumor Necrosis Factor-alpha analysis
Tumor Necrosis Factor-alpha metabolism
Bacterial Translocation drug effects
Colon drug effects
Intestinal Mucosa drug effects
Lipopolysaccharides pharmacology
Myosin-Light-Chain Kinase metabolism
Tight Junctions drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 167
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 16192642
- Full Text :
- https://doi.org/10.1016/S0002-9440(10)61196-0