The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2)
The mast cell product tryptase, via protease-activated receptor 2 (PAR2), induces cyclooxygenase-2 (COX2) and 15-deoxy-prostaglandin J2 (15d-PGJ2) synthesis. 15d-PGJ2, through the nuclear peroxisome proliferator activated receptor gamma (PPARγ), subsequently causes fibroblast proliferation. In this...
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todo:paper_08986568_v17_n4_p525_Frungieri2023-10-03T15:44:01Z The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) Frungieri, M.B. Albrecht, M. Raemsch, R. Mayerhofer, A. Ca 2+ cAMP Cyclooxygenase-2 MAP kinases Transcription factors Tryptase 2 (2 amino 3 methoxyphenyl)chromone cyclooxygenase 2 mitogen activated protein kinase 1 mitogen activated protein kinase inhibitor phosphotransferase prostaglandin derivative protein c fos stress activated protein kinase tryptase article calcium cell level cell proliferation controlled study DNA microarray enzyme activation enzyme activity enzyme induction enzyme mechanism fibroblast human human cell mast cell priority journal protein expression protein phosphorylation reverse transcription polymerase chain reaction signal transduction upregulation Western blotting Base Sequence Calcium Cell Proliferation Cyclic AMP Cyclooxygenase 2 Fibroblasts Humans Male Mast Cells Membrane Proteins Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Protein Isoforms Serine Endopeptidases Signal Transduction Tryptases Up-Regulation The mast cell product tryptase, via protease-activated receptor 2 (PAR2), induces cyclooxygenase-2 (COX2) and 15-deoxy-prostaglandin J2 (15d-PGJ2) synthesis. 15d-PGJ2, through the nuclear peroxisome proliferator activated receptor gamma (PPARγ), subsequently causes fibroblast proliferation. In this study we attempted to determine initial events of the tryptase/PAR2 signaling pathway leading to COX2 induction and fibroblast proliferation. In human fibroblasts (HFFF2), cDNA array, RT-PCR and Western blotting studies demonstrated that tryptase, but not 15d-PGJ2, up-regulates c-jun, c-fos and COX2 expression, and phosphorylates the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Furthermore, tryptase effects on erk1/2, c-jun, c-fos, COX2 and cell proliferation were prevented by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK). Other kinases [P38, stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JUNK), erk5], intracellular Ca 2+ or cAMP were not affected by tryptase/PAR2. Our study identifies crucial intracellular events leading to induction of COX2 and fibroblast proliferation, i.e. a cornerstone of fibrosis. © 2004 Elsevier Inc. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08986568_v17_n4_p525_Frungieri |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Ca 2+ cAMP Cyclooxygenase-2 MAP kinases Transcription factors Tryptase 2 (2 amino 3 methoxyphenyl)chromone cyclooxygenase 2 mitogen activated protein kinase 1 mitogen activated protein kinase inhibitor phosphotransferase prostaglandin derivative protein c fos stress activated protein kinase tryptase article calcium cell level cell proliferation controlled study DNA microarray enzyme activation enzyme activity enzyme induction enzyme mechanism fibroblast human human cell mast cell priority journal protein expression protein phosphorylation reverse transcription polymerase chain reaction signal transduction upregulation Western blotting Base Sequence Calcium Cell Proliferation Cyclic AMP Cyclooxygenase 2 Fibroblasts Humans Male Mast Cells Membrane Proteins Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Protein Isoforms Serine Endopeptidases Signal Transduction Tryptases Up-Regulation |
spellingShingle |
Ca 2+ cAMP Cyclooxygenase-2 MAP kinases Transcription factors Tryptase 2 (2 amino 3 methoxyphenyl)chromone cyclooxygenase 2 mitogen activated protein kinase 1 mitogen activated protein kinase inhibitor phosphotransferase prostaglandin derivative protein c fos stress activated protein kinase tryptase article calcium cell level cell proliferation controlled study DNA microarray enzyme activation enzyme activity enzyme induction enzyme mechanism fibroblast human human cell mast cell priority journal protein expression protein phosphorylation reverse transcription polymerase chain reaction signal transduction upregulation Western blotting Base Sequence Calcium Cell Proliferation Cyclic AMP Cyclooxygenase 2 Fibroblasts Humans Male Mast Cells Membrane Proteins Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Protein Isoforms Serine Endopeptidases Signal Transduction Tryptases Up-Regulation Frungieri, M.B. Albrecht, M. Raemsch, R. Mayerhofer, A. The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
topic_facet |
Ca 2+ cAMP Cyclooxygenase-2 MAP kinases Transcription factors Tryptase 2 (2 amino 3 methoxyphenyl)chromone cyclooxygenase 2 mitogen activated protein kinase 1 mitogen activated protein kinase inhibitor phosphotransferase prostaglandin derivative protein c fos stress activated protein kinase tryptase article calcium cell level cell proliferation controlled study DNA microarray enzyme activation enzyme activity enzyme induction enzyme mechanism fibroblast human human cell mast cell priority journal protein expression protein phosphorylation reverse transcription polymerase chain reaction signal transduction upregulation Western blotting Base Sequence Calcium Cell Proliferation Cyclic AMP Cyclooxygenase 2 Fibroblasts Humans Male Mast Cells Membrane Proteins Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Protein Isoforms Serine Endopeptidases Signal Transduction Tryptases Up-Regulation |
description |
The mast cell product tryptase, via protease-activated receptor 2 (PAR2), induces cyclooxygenase-2 (COX2) and 15-deoxy-prostaglandin J2 (15d-PGJ2) synthesis. 15d-PGJ2, through the nuclear peroxisome proliferator activated receptor gamma (PPARγ), subsequently causes fibroblast proliferation. In this study we attempted to determine initial events of the tryptase/PAR2 signaling pathway leading to COX2 induction and fibroblast proliferation. In human fibroblasts (HFFF2), cDNA array, RT-PCR and Western blotting studies demonstrated that tryptase, but not 15d-PGJ2, up-regulates c-jun, c-fos and COX2 expression, and phosphorylates the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Furthermore, tryptase effects on erk1/2, c-jun, c-fos, COX2 and cell proliferation were prevented by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK). Other kinases [P38, stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JUNK), erk5], intracellular Ca 2+ or cAMP were not affected by tryptase/PAR2. Our study identifies crucial intracellular events leading to induction of COX2 and fibroblast proliferation, i.e. a cornerstone of fibrosis. © 2004 Elsevier Inc. All rights reserved. |
format |
JOUR |
author |
Frungieri, M.B. Albrecht, M. Raemsch, R. Mayerhofer, A. |
author_facet |
Frungieri, M.B. Albrecht, M. Raemsch, R. Mayerhofer, A. |
author_sort |
Frungieri, M.B. |
title |
The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
title_short |
The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
title_full |
The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
title_fullStr |
The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
title_full_unstemmed |
The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
title_sort |
action of the mast cell product tryptase on cyclooxygenase-2 (cox2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2) |
url |
http://hdl.handle.net/20.500.12110/paper_08986568_v17_n4_p525_Frungieri |
work_keys_str_mv |
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1807318405592645632 |