Rho Kinases in Autoimmune Diseases

Annu Rev Med. 2016:67:355-74. doi: 10.1146/annurev-med-051914-022120.

Abstract

The Rho kinases, or ROCKs, are a family of serine-threonine kinases that serve as key downstream effectors for Rho GTPases. The ROCKs are increasingly recognized as critical coordinators of a tissue response to injury due to their ability to modulate a wide range of biological processes. Dysregulated ROCK activity has been implicated in several human pathophysiological conditions ranging from cardiovascular and renal disorders to fibrotic diseases. In recent years, an important role for the ROCKs in the regulation of immune responses is also being uncovered. We provide an overview of the role of the ROCKs in immune cells and discuss studies that highlight the emerging involvement of this family of kinases in the pathogenesis of autoimmune diseases. Given the potential promise of the ROCKs as therapeutic targets, we also outline the approaches that could be employed to inhibit the ROCKs in autoimmune disorders.

Keywords: autoimmunity; cytoskeletal reorganization; inflammation; interleukin 17; interleukin 21; kinase inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Amides / therapeutic use
  • Animals
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism*
  • B-Lymphocytes / immunology
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cytoskeleton / metabolism
  • Gene Expression
  • Giant Cell Arteritis / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • Myeloid Cells / immunology
  • Osteoarthritis / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / therapeutic use
  • Scleroderma, Systemic / drug therapy
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / metabolism
  • T-Lymphocytes / immunology*
  • rho GTP-Binding Proteins / metabolism*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / drug effects
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / immunology*
  • rho-Associated Kinases / metabolism*

Substances

  • Amides
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Protein Kinase Inhibitors
  • Pyridines
  • Y 27632
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • rho-Associated Kinases
  • rho GTP-Binding Proteins
  • fasudil