A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA

S H Ridley; J L Dean; S J Sarsfield; M Brook; A R Clark; J Saklatvala

A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA

S H Ridley, J L Dean, S J Sarsfield, M Brook, A R Clark, J Saklatvala

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 microM inhibited IL-1-stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA. IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.

Original language	English
Pages (from-to)	75-80
Number of pages	6
Journal	FEBS Letters
Volume	439
Issue number	1-2
Publication status	Published - 13 Nov 1998

Keywords / Materials (for Non-textual outputs)

Arachidonic Acids
Calcium-Calmodulin-Dependent Protein Kinases
Cyclooxygenase 2
Dinoprostone
Enzyme Induction
Enzyme Inhibitors
HeLa Cells
Humans
Imidazoles
Interleukin-1
Isoenzymes
JNK Mitogen-Activated Protein Kinases
Membrane Proteins
Mitogen-Activated Protein Kinases
Prostaglandin-Endoperoxide Synthases
Pyridines
RNA, Messenger
p38 Mitogen-Activated Protein Kinases

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@article{eaffb71377dc4547b6153ed8ea5f67fb,

title = "A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA",

abstract = "The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 microM inhibited IL-1-stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA. IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.",

keywords = "Arachidonic Acids, Calcium-Calmodulin-Dependent Protein Kinases, Cyclooxygenase 2, Dinoprostone, Enzyme Induction, Enzyme Inhibitors, HeLa Cells, Humans, Imidazoles, Interleukin-1, Isoenzymes, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Mitogen-Activated Protein Kinases, Prostaglandin-Endoperoxide Synthases, Pyridines, RNA, Messenger, p38 Mitogen-Activated Protein Kinases",

author = "Ridley, {S H} and Dean, {J L} and Sarsfield, {S J} and M Brook and Clark, {A R} and J Saklatvala",

year = "1998",

month = nov,

day = "13",

language = "English",

volume = "439",

pages = "75--80",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA

AU - Ridley, S H

AU - Dean, J L

AU - Sarsfield, S J

AU - Brook, M

AU - Clark, A R

AU - Saklatvala, J

PY - 1998/11/13

Y1 - 1998/11/13

N2 - The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 microM inhibited IL-1-stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA. IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.

AB - The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 microM inhibited IL-1-stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA. IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.

KW - Arachidonic Acids

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Cyclooxygenase 2

KW - Dinoprostone

KW - Enzyme Induction

KW - Enzyme Inhibitors

KW - HeLa Cells

KW - Humans

KW - Imidazoles

KW - Interleukin-1

KW - Isoenzymes

KW - JNK Mitogen-Activated Protein Kinases

KW - Membrane Proteins

KW - Mitogen-Activated Protein Kinases

KW - Prostaglandin-Endoperoxide Synthases

KW - Pyridines

KW - RNA, Messenger

KW - p38 Mitogen-Activated Protein Kinases

M3 - Article

C2 - 9849881

SN - 0014-5793

VL - 439

SP - 75

EP - 80

JO - FEBS Letters

JF - FEBS Letters

IS - 1-2

ER -

A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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