Leukotriene D-4 induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKC delta
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/329192
- author
- Massoumi, Ramin LU ; Larsson, Christer LU and Sjölander, Anita LU
- organization
- publishing date
- 2002
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Tumour Cell Biology (013017530), Cell Pathology (013031400)
- 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
- 2016-04-01 11:47:48
- date last changed
- 2021-09-27 04:09:50
@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}}, keywords = {{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}}, url = {{http://jcs.biologists.org.ludwig.lub.lu.se/cgi/reprint/115/17/3509}}, volume = {{115}}, year = {{2002}}, }