Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects

Int Immunopharmacol. 2004 Apr;4(4):557-61. doi: 10.1016/j.intimp.2003.12.014.

Abstract

Previously we have reported that Y-27632, a selective inhibitor of Rho-associated protein kinases (ROCKs) for RhoA, suppressed concanavalin A (Con A)-induced secretion of cytokines from peripheral T cells of normal persons. Recent studies suggested its usefulness for clinical management of bronchial asthma. We examined effect of Y-27632 on release of cytokines from T cells of asthmatic patients. Peripheral T cells of six asthmatic subjects and six normal persons were stimulated with Con A for 24 h in the presence of Y-27632. The concentrations of IL-2, interferon (IFN)-gamma, IL-4, and IL-5 in supernatant were measured. Y-27632 down-regulated secretion of IL-2 and IFN-gamma and weakly decreased secretion of IL-4 and IL-5 from Con A-activated T cells in the asthmatics. The reduced secretion of IFN-gamma and IL-4 in the asthmatics was inferior to that in the normal subjects. Our data suggested that the involvement of RhoA/ROCK pathway in TCR-mediated secretion of IFN-gamma and IL-4 in patients with bronchial asthma differed from that in healthy persons.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Amides / administration & dosage
  • Amides / pharmacology*
  • Asthma / immunology
  • Asthma / metabolism*
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Cytokines / biosynthesis*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • rho-Associated Kinases

Substances

  • Amides
  • Cytokines
  • Interleukin-2
  • Interleukin-5
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • Concanavalin A
  • Y 27632
  • Interleukin-4
  • Interferon-gamma
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases