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Leukotriene D-4 induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKC delta

Massoumi, Ramin LU ; Larsson, Christer LU and Sjölander, Anita LU (2002) In Journal of Cell Science 115(17). p.3509-3515
Abstract
The intestinal epithelial barrier, which is regulated by the actin cytoskeleton, exhibits permeability changes during inflammation. Here we show that activation of the CysLT(1) receptor by the inflammatory mediator leukotriene D-4 (LTD4) causes a rapid increase in stress-fibre formation in intestinal epithelial cells. This effect was mimicked by cytotoxic necrotising factor-1 (CNF-1)-induced activation of RhoA, overexpression of constitutively active RhoA (L63-RhoA) and phorbol-ester-induced activation of protein kinase C (PKC). In accordance, inhibition of RhoA, by C3 exoenzyme or by dominant-negative RhoA (N19-RhoA), as well as GF109203X-induced inhibition of PKC, suppressed the LTD4-induced stress-fibre formation. Introduction of the... (More)
The intestinal epithelial barrier, which is regulated by the actin cytoskeleton, exhibits permeability changes during inflammation. Here we show that activation of the CysLT(1) receptor by the inflammatory mediator leukotriene D-4 (LTD4) causes a rapid increase in stress-fibre formation in intestinal epithelial cells. This effect was mimicked by cytotoxic necrotising factor-1 (CNF-1)-induced activation of RhoA, overexpression of constitutively active RhoA (L63-RhoA) and phorbol-ester-induced activation of protein kinase C (PKC). In accordance, inhibition of RhoA, by C3 exoenzyme or by dominant-negative RhoA (N19-RhoA), as well as GF109203X-induced inhibition of PKC, suppressed the LTD4-induced stress-fibre formation. Introduction of the dominant-negative regulatory domain of PKCdelta, but not the corresponding structures from PKCalpha, betaII or epsilon, blocked the LTD4-induced stress-fibre formation. Evaluating the relationship between PKCdelta and RhoA in LTD4-induced stress-fibre formation, we found that C3 exoenzyme inhibited the rapid LTD4-elicited translocation of PKCdelta to the plasma membrane. Furthermore, CNF-1-induced stress-fibre formation was blocked by GF109203X and by overexpression of the regulatory domain of PKC-delta, whereas PKC-induced stress-fibre production was not affected by N19-RhoA. We conclude that PKC-delta is located downstream of RhoA and that active RhoA and PKCdelta are both necessary for LTD4-induced stress-fibre formation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
RhoA, stress fibres, PKC-delta, LTD4, CNF-1
in
Journal of Cell Science
volume
115
issue
17
pages
3509 - 3515
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:12154081
  • wos:000177884500015
ISSN
0021-9533
language
English
LU publication?
yes
id
a0090b47-94ce-453b-9412-f151ac7d6530 (old id 329192)
alternative location
http://jcs.biologists.org.ludwig.lub.lu.se/cgi/reprint/115/17/3509
date added to LUP
2007-11-02 11:25:26
date last changed
2016-04-15 19:04:21
@article{a0090b47-94ce-453b-9412-f151ac7d6530,
  abstract     = {The intestinal epithelial barrier, which is regulated by the actin cytoskeleton, exhibits permeability changes during inflammation. Here we show that activation of the CysLT(1) receptor by the inflammatory mediator leukotriene D-4 (LTD4) causes a rapid increase in stress-fibre formation in intestinal epithelial cells. This effect was mimicked by cytotoxic necrotising factor-1 (CNF-1)-induced activation of RhoA, overexpression of constitutively active RhoA (L63-RhoA) and phorbol-ester-induced activation of protein kinase C (PKC). In accordance, inhibition of RhoA, by C3 exoenzyme or by dominant-negative RhoA (N19-RhoA), as well as GF109203X-induced inhibition of PKC, suppressed the LTD4-induced stress-fibre formation. Introduction of the dominant-negative regulatory domain of PKCdelta, but not the corresponding structures from PKCalpha, betaII or epsilon, blocked the LTD4-induced stress-fibre formation. Evaluating the relationship between PKCdelta and RhoA in LTD4-induced stress-fibre formation, we found that C3 exoenzyme inhibited the rapid LTD4-elicited translocation of PKCdelta to the plasma membrane. Furthermore, CNF-1-induced stress-fibre formation was blocked by GF109203X and by overexpression of the regulatory domain of PKC-delta, whereas PKC-induced stress-fibre production was not affected by N19-RhoA. We conclude that PKC-delta is located downstream of RhoA and that active RhoA and PKCdelta are both necessary for LTD4-induced stress-fibre formation.},
  author       = {Massoumi, Ramin and Larsson, Christer and Sjölander, Anita},
  issn         = {0021-9533},
  keyword      = {RhoA,stress fibres,PKC-delta,LTD4,CNF-1},
  language     = {eng},
  number       = {17},
  pages        = {3509--3515},
  publisher    = {The Company of Biologists Ltd},
  series       = {Journal of Cell Science},
  title        = {Leukotriene D-4 induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKC delta},
  volume       = {115},
  year         = {2002},
}