Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease

Stephanie A. Blair, Sunanda V. Kane, Daniel Clayburgh, Jerrold R. Turner

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalLaboratory Investigation
Volume86
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Fingerprint

Myosin-Light-Chain Kinase
Inflammatory Bowel Diseases
Phosphorylation
Biopsy
Myosin Type II
Myosin Light Chains
Intestinal Mucosa
Fluorescence Microscopy
Colon
Up-Regulation
Cytokines

Keywords

  • Crohn's disease
  • Myosin
  • Tight junctions
  • Tumor necrosis factor
  • Ulcerative colitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. / Blair, Stephanie A.; Kane, Sunanda V.; Clayburgh, Daniel; Turner, Jerrold R.

In: Laboratory Investigation, Vol. 86, No. 2, 02.2006, p. 191-201.

Research output: Contribution to journalArticle

Blair, Stephanie A. ; Kane, Sunanda V. ; Clayburgh, Daniel ; Turner, Jerrold R. / Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. In: Laboratory Investigation. 2006 ; Vol. 86, No. 2. pp. 191-201.
@article{f3d6548334a34be48f776bd8f49317f3,
title = "Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease",
abstract = "The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.",
keywords = "Crohn's disease, Myosin, Tight junctions, Tumor necrosis factor, Ulcerative colitis",
author = "Blair, {Stephanie A.} and Kane, {Sunanda V.} and Daniel Clayburgh and Turner, {Jerrold R.}",
year = "2006",
month = "2",
doi = "10.1038/labinvest.3700373",
language = "English (US)",
volume = "86",
pages = "191--201",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease

AU - Blair, Stephanie A.

AU - Kane, Sunanda V.

AU - Clayburgh, Daniel

AU - Turner, Jerrold R.

PY - 2006/2

Y1 - 2006/2

N2 - The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.

AB - The intestinal epithelial barrier is frequently disrupted in inflammatory bowel disease (IBD) and this has been proposed to play a role in disease pathogenesis and reactivation. In vitro studies show that cytokine-induced epithelial barrier dysfunction can be mediated by increased myosin light chain kinase (MLCK) expression and subsequent myosin II regulatory light chain (MLC) phosphorylation. However, this has never been examined in human disease. The aim of these studies, therefore, was to determine whether MLCK is upregulated in the intestinal epithelium of IBD patients. MLCK expression and MLC phosphorylation in human intestinal resection and biopsy specimens were determined by quantitative immunofluorescence microscopy and correlated with clinical and histopathological data. The data show that ileal epithelial MLCK expression was mildly upregulated in inactive IBD. Expression increased further in active disease, with progressive increases in MLCK expression correlating positively with histological disease activity. This correlation between activity and MLCK expression was also seen in individual patients where areas of differing disease activity were analyzed. Colonic epithelial MLCK expression was similarly increased in active IBD and these increases also correlated positively with disease activity, both in individual patients and the overall study group. To evaluate MLCK enzymatic activity, MLC phosphorylation was assessed in snap-frozen colon biopsies. MLC phosphorylation was significantly increased in biopsies with active, but not inactive, IBD. Therefore, these data show that MLCK expression and enzymatic activity are increased in IBD. Moreover, the correlation with disease activity suggests that MLCK upregulation may contribute to barrier dysfunction and IBD pathogenesis.

KW - Crohn's disease

KW - Myosin

KW - Tight junctions

KW - Tumor necrosis factor

KW - Ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=30944443377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30944443377&partnerID=8YFLogxK

U2 - 10.1038/labinvest.3700373

DO - 10.1038/labinvest.3700373

M3 - Article

VL - 86

SP - 191

EP - 201

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 2

ER -