Superinduction of COX-2 mRNA by cycloheximide and interleukin-1β involves increased transcription and correlates with increased NF-κB and JNK activation

Robert Newton; David A. Stevens; Lorraine A. Hart; Mark Lindsay; Ian M. Adcock; Peter J. Barnes

doi:10.1016/S0014-5793(97)01362-8

Superinduction of COX-2 mRNA by cycloheximide and interleukin-1β involves increased transcription and correlates with increased NF-κB and JNK activation

Robert Newton, David A. Stevens, Lorraine A. Hart, Mark Lindsay, Ian M. Adcock, Peter J. Barnes

Imperial College London

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

105 Citations (SciVal)

Abstract

Many primary response genes, including cyclooxy-genase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1β-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-κB binding to COX-2 promoter κB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-κB by de novo IκBα synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

Original language	English
Pages (from-to)	135-138
Number of pages	4
Journal	FEBS Letters
Volume	418
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(97)01362-8
Publication status	Published - 24 Nov 1997

Bibliographical note

Funding Information:
This work was supported by grants from the British Lung Foundation, the Medical Research Council, the National Asthma Campaign, the Wellcome Trust and the European Commission. Bacterially expressed GST-c-Jun (1-135) was given by Peter Sugden.

Funding

This work was supported by grants from the British Lung Foundation, the Medical Research Council, the National Asthma Campaign, the Wellcome Trust and the European Commission. Bacterially expressed GST-c-Jun (1-135) was given by Peter Sugden.

Keywords

Cycloheximide
Cyclooxygenase
Jun N-terminal kinase
Nuclear factor-κB
Prostaglandin G/H synthase
Superinduction

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "Superinduction of COX-2 mRNA by cycloheximide and interleukin-1β involves increased transcription and correlates with increased NF-κB and JNK activation",

abstract = "Many primary response genes, including cyclooxy-genase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1β-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-κB binding to COX-2 promoter κB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-κB by de novo IκBα synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.",

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author = "Robert Newton and Stevens, \{David A.\} and Hart, \{Lorraine A.\} and Mark Lindsay and Adcock, \{Ian M.\} and Barnes, \{Peter J.\}",

note = "Funding Information: This work was supported by grants from the British Lung Foundation, the Medical Research Council, the National Asthma Campaign, the Wellcome Trust and the European Commission. Bacterially expressed GST-c-Jun (1-135) was given by Peter Sugden.",

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AU - Stevens, David A.

AU - Hart, Lorraine A.

AU - Lindsay, Mark

AU - Adcock, Ian M.

AU - Barnes, Peter J.

N1 - Funding Information: This work was supported by grants from the British Lung Foundation, the Medical Research Council, the National Asthma Campaign, the Wellcome Trust and the European Commission. Bacterially expressed GST-c-Jun (1-135) was given by Peter Sugden.

PY - 1997/11/24

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N2 - Many primary response genes, including cyclooxy-genase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1β-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-κB binding to COX-2 promoter κB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-κB by de novo IκBα synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

AB - Many primary response genes, including cyclooxy-genase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1β-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-κB binding to COX-2 promoter κB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-κB by de novo IκBα synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

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KW - Cyclooxygenase

KW - Jun N-terminal kinase

KW - Nuclear factor-κB

KW - Prostaglandin G/H synthase

KW - Superinduction

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Superinduction of COX-2 mRNA by cycloheximide and interleukin-1β involves increased transcription and correlates with increased NF-κB and JNK activation

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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