Targeting Rho-GTPases in immune cell migration and inflammation
Leukocytes are unmatched migrators capable of traversing barriers and tissues of remarkably varied structural composition. An effective immune response relies on the ability of its constituent cells to infiltrate target sites. Yet, unwarranted mobilization of immune cells can lead to inflammatory di...
| Main Authors: | , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
BlackWell Publishing Ltd
2014
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282076/ |
| id |
pubmed-4282076 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-42820762015-01-15 Targeting Rho-GTPases in immune cell migration and inflammation Biro, Maté Munoz, Marcia A Weninger, Wolfgang Themed Section: Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics Leukocytes are unmatched migrators capable of traversing barriers and tissues of remarkably varied structural composition. An effective immune response relies on the ability of its constituent cells to infiltrate target sites. Yet, unwarranted mobilization of immune cells can lead to inflammatory diseases and tissue damage ranging in severity from mild to life-threatening. The efficacy and plasticity of leukocyte migration is driven by the precise spatiotemporal regulation of the actin cytoskeleton. The small GTPases of the Rho family (Rho-GTPases), and their immediate downstream effector kinases, are key regulators of cellular actomyosin dynamics and are therefore considered prime pharmacological targets for stemming leukocyte motility in inflammatory disorders. This review describes advances in the development of small-molecule inhibitors aimed at modulating the Rho-GTPase-centric regulatory pathways governing motility, many of which stem from studies of cancer invasiveness. These inhibitors promise the advent of novel treatment options with high selectivity and potency against immune-mediated pathologies. BlackWell Publishing Ltd 2014-12 2014-07-02 /pmc/articles/PMC4282076/ /pubmed/24571448 http://dx.doi.org/10.1111/bph.12658 Text en Copyright © 2014 The British Pharmacological Society http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Biro, Maté Munoz, Marcia A Weninger, Wolfgang |
| spellingShingle |
Biro, Maté Munoz, Marcia A Weninger, Wolfgang Targeting Rho-GTPases in immune cell migration and inflammation |
| author_facet |
Biro, Maté Munoz, Marcia A Weninger, Wolfgang |
| author_sort |
Biro, Maté |
| title |
Targeting Rho-GTPases in immune cell migration and inflammation |
| title_short |
Targeting Rho-GTPases in immune cell migration and inflammation |
| title_full |
Targeting Rho-GTPases in immune cell migration and inflammation |
| title_fullStr |
Targeting Rho-GTPases in immune cell migration and inflammation |
| title_full_unstemmed |
Targeting Rho-GTPases in immune cell migration and inflammation |
| title_sort |
targeting rho-gtpases in immune cell migration and inflammation |
| description |
Leukocytes are unmatched migrators capable of traversing barriers and tissues of remarkably varied structural composition. An effective immune response relies on the ability of its constituent cells to infiltrate target sites. Yet, unwarranted mobilization of immune cells can lead to inflammatory diseases and tissue damage ranging in severity from mild to life-threatening. The efficacy and plasticity of leukocyte migration is driven by the precise spatiotemporal regulation of the actin cytoskeleton. The small GTPases of the Rho family (Rho-GTPases), and their immediate downstream effector kinases, are key regulators of cellular actomyosin dynamics and are therefore considered prime pharmacological targets for stemming leukocyte motility in inflammatory disorders. This review describes advances in the development of small-molecule inhibitors aimed at modulating the Rho-GTPase-centric regulatory pathways governing motility, many of which stem from studies of cancer invasiveness. These inhibitors promise the advent of novel treatment options with high selectivity and potency against immune-mediated pathologies. |
| publisher |
BlackWell Publishing Ltd |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282076/ |
| _version_ |
1613172565517271040 |