ROCK mediates the inflammatory response in thrombin induced microglia

Neurosci Lett. 2013 Oct 25:554:82-7. doi: 10.1016/j.neulet.2013.08.065. Epub 2013 Sep 7.

Abstract

To investigate whether the ROCK pathway is involved in thrombin-induced microglial inflammatory response, thrombin-induced microglia were pretreated with the thrombin inhibitor argatroban or a ROCK inhibitor Y-27632. Microglial inflammatory response was evaluated by phagocytosis of fluorescein labeled latex beads analyses and inflammatory mediators' expression such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-а). Compared to non-induced microglia, thrombin-induced microglia show significantly enhanced phagocytotic capacity and increased ROCK, NO and TNF-а expression. Pretreatment of thrombin-induced microglia with argatroban or Y-27632 significantly decreased phagocytotic capacity and reduced ROCK, NO and TNF-α expression. Therefore, the ROCK pathway may play a vital role in the mechanisms by which thrombin induces microglia in the inflammatory response.

Keywords: Argatroban; Inflammation; Microglia; ROCK; Y-27632.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Antithrombins / pharmacology
  • Arginine / analogs & derivatives
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Fluorescein
  • Fluorescent Dyes
  • Inflammation / immunology
  • Inflammation / metabolism
  • Microglia / immunology
  • Microglia / metabolism*
  • Microspheres
  • Nitric Oxide / metabolism
  • Phagocytosis
  • Pipecolic Acids / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides
  • Thrombin / immunology
  • Thrombin / metabolism*
  • Thrombin / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism*

Substances

  • Amides
  • Antithrombins
  • Fluorescent Dyes
  • Pipecolic Acids
  • Pyridines
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Y 27632
  • Nitric Oxide
  • Arginine
  • rho-Associated Kinases
  • Thrombin
  • argatroban
  • Fluorescein