Activation of the extracellular signal-regulated kinase pathway is differentially required for TCR-stimulated production of six cytokines in primary T lymphocytes |
| |
Authors: | Egerton M; Fitzpatrick DR; Kelso A |
| |
Institution: | The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia. |
| |
Abstract: | The extracellular signal-regulated kinase (ERK) signaling pathway is
strongly activated in response to TCR stimulation in normal T cells.
However, the extent to which activation of the ERK pathway is necessary for
TCR-stimulated cytokine production is not clear. We have addressed this
question by use of two separate methods to interfere with TCR activation of
the ERK cascade. The first approach utilized transient expression of a
catalytically inactive form of mitogen-activated/ERK 1 (CI-MEK1), while the
second involved using the MEK1- and MEK2-specific inhibitor PD98059 to
block ERK activation by the TCR. In order to assess the requirement for ERK
activation in T cell cytokine production, we have measured the effect of
ERK inhibition upon the production of six cytokines, IL-3, IL-4, IL-5,
IL-10, granulocyte macrophage colony stimulating factor (GM-CSF) and
IFN-gamma, by newly activated normal mouse T cells in response to TCR
stimulation. The results of experiments using both methods to block ERK
activation have revealed a requirement for intact ERK signaling for the
full elicitation of TCR-stimulated cytokine production. Dose-response
analyses using the MEK inhibitor PD98059 showed that the TCR-stimulated
production of all cytokines measured was affected by this treatment.
However, the production of IL-3 and IL-4 was only partially dependent upon
ERK activation, whereas IL-5, IL-10, IFN-gamma and GM-CSF production was
severely affected by diminished ERK activation. We conclude that the ERK
pathway is differentially involved in the activation of different cytokine
genes in normal T cells.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|