Advanced

Leukotriene D(4) induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKCdelta.

Massoumi, Ramin LU ; Larsson, Christer and Sjölander, Anita LU (2002) In Journal of Cell Science 115(Pt 17). p.15-3509
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) (LTD(4)) 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 LTD(4)-induced stress-fibre formation. Introduction of... (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) (LTD(4)) 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 LTD(4)-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 LTD(4)-induced stress-fibre formation. Evaluating the relationship between PKCdelta and RhoA in LTD(4)-induced stress-fibre formation, we found that C3 exoenzyme inhibited the rapid LTD(4)-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 LTD(4)-induced stress-fibre formation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cell Science
volume
115
issue
Pt 17
pages
15 - 3509
publisher
The Company of Biologists Ltd
ISSN
0021-9533
language
English
LU publication?
yes
id
1fe5c55a-4cf6-4f36-9a96-bdb18df758a6 (old id 109717)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12154081&dopt=Abstract
date added to LUP
2007-07-26 08:56:51
date last changed
2016-04-15 18:41:33
@article{1fe5c55a-4cf6-4f36-9a96-bdb18df758a6,
  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) (LTD(4)) 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 LTD(4)-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 LTD(4)-induced stress-fibre formation. Evaluating the relationship between PKCdelta and RhoA in LTD(4)-induced stress-fibre formation, we found that C3 exoenzyme inhibited the rapid LTD(4)-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 LTD(4)-induced stress-fibre formation.},
  author       = {Massoumi, Ramin and Larsson, Christer and Sjölander, Anita},
  issn         = {0021-9533},
  language     = {eng},
  number       = {Pt 17},
  pages        = {15--3509},
  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 PKCdelta.},
  volume       = {115},
  year         = {2002},
}