Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. Academic Article uri icon

Overview

MeSH

  • Animals
  • Caspase 8
  • Caspase Inhibitors
  • Cells, Cultured
  • Cyclic GMP
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Activation
  • Enzyme Inhibitors
  • Guanylate Cyclase
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase Kinase 3
  • MAP Kinase Kinase Kinases
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases
  • Up-Regulation

MeSH Major

  • Carbon Monoxide
  • Caspases
  • Growth Inhibitors
  • Immunosuppressive Agents
  • JNK Mitogen-Activated Protein Kinases
  • T-Lymphocytes

abstract

  • T lymphocyte activation and proliferation is involved in many pathological processes. We have recently shown that carbon monoxide (CO), an enzymatic product of heme oxygenase-1 (HO-1), confers potent antiproliferative effects in airway and vascular smooth muscle cells. The purpose of this study was to determine whether CO can inhibit T lymphocyte proliferation and then to determine the mechanism by which CO can modulate T lymphocyte proliferation. In the presence of 250 parts per million CO, CD3-activated T lymphocyte proliferation was, remarkably, inhibited by 80% when compared with controls. We observed that the antiproliferative effect of CO in T lymphocytes was independent of the mitogen-activated protein kinase or cGMP signaling pathways, unlike what we demonstrated previously in smooth muscle cells. We demonstrate that CO inhibited caspase-3 and caspase-8 expression and activity, and caspase inhibition with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK pan-caspase inhibitor) blocked T lymphocyte proliferation. Furthermore, in caspase-8-deficient lymphocytes, the antiproliferative effect of CO was markedly attenuated, further supporting the involvement of caspase-8 in the antiproliferative effects of CO. CO also increased the protein level of p21(Cip1), and CO-mediated inhibition of caspase activity is partially regulated by p21(Cip1). Taken together, these data suggest that CO confers potent antiproliferative effects in CD3-activated T lymphocytes and that these antiproliferative effects in T lymphocytes are mediated by p21(Cip1)-dependent caspase activity, in particular caspase-8, independent of cGMP and mitogen-activated protein kinase signaling pathways.

publication date

  • January 15, 2004

has subject area

  • Animals
  • Carbon Monoxide
  • Caspase 8
  • Caspase Inhibitors
  • Caspases
  • Cells, Cultured
  • Cyclic GMP
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Activation
  • Enzyme Inhibitors
  • Growth Inhibitors
  • Guanylate Cyclase
  • Humans
  • Immunosuppressive Agents
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase Kinase 3
  • MAP Kinase Kinase Kinases
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases
  • T-Lymphocytes
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 14707100

Additional Document Info

start page

  • 1220

end page

  • 1226

volume

  • 172

number

  • 2