title: Targeting Rho-GTPases in immune cell migration and inflammation.
abstract: 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.
  
  
  BACKGROUND
  This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Immune Imaging Program, Newtown, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Maté
authors.initials: M
authors.lastname: Biro
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Munoz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D009218:Myosins / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases; D009218:Myosins; D020741:rho GTP-Binding Proteins