Eintrag weiter verarbeiten
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway
Gespeichert in:
Zeitschriftentitel: | Journal of Leukocyte Biology |
---|---|
Personen und Körperschaften: | , |
In: | Journal of Leukocyte Biology, 78, 2005, 1, S. 259-265 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Oxford University Press (OUP)
|
Schlagwörter: |
author_facet |
Lu, Yunbiao Wahl, Larry M Lu, Yunbiao Wahl, Larry M |
---|---|
author |
Lu, Yunbiao Wahl, Larry M |
spellingShingle |
Lu, Yunbiao Wahl, Larry M Journal of Leukocyte Biology Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway Cell Biology Immunology Immunology and Allergy |
author_sort |
lu, yunbiao |
spelling |
Lu, Yunbiao Wahl, Larry M 0741-5400 1938-3673 Oxford University Press (OUP) Cell Biology Immunology Immunology and Allergy http://dx.doi.org/10.1189/jlb.0904498 <jats:title>Abstract</jats:title><jats:p>Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as lipopolysaccharide (LPS) or tumor necrosis factor α and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidylinositol-3 kinase (PI-3K)/Akt/inhibitor of κB (IκB) kinase-α (IKKα)/nuclear factor (NF)-κB pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of PI-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-κB, as shown by coimmunoprecipitation of the phosphorylated form of IKKα and Akt as well as the SH-5 suppression of the dissociation of IκB from NF-κB and the activation of NF-κB p65. The role of NF-κB in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of IκB from NF-κB. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes.</jats:p> Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway Journal of Leukocyte Biology |
doi_str_mv |
10.1189/jlb.0904498 |
facet_avail |
Online Free |
finc_class_facet |
Biologie Medizin |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4OS9qbGIuMDkwNDQ5OA |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4OS9qbGIuMDkwNDQ5OA |
institution |
DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 |
imprint |
Oxford University Press (OUP), 2005 |
imprint_str_mv |
Oxford University Press (OUP), 2005 |
issn |
0741-5400 1938-3673 |
issn_str_mv |
0741-5400 1938-3673 |
language |
English |
mega_collection |
Oxford University Press (OUP) (CrossRef) |
match_str |
lu2005productionofmatrixmetalloproteinase9byactivatedhumanmonocytesinvolvesaphosphatidylinositol3kinaseaktikkanfkbpathway |
publishDateSort |
2005 |
publisher |
Oxford University Press (OUP) |
recordtype |
ai |
record_format |
ai |
series |
Journal of Leukocyte Biology |
source_id |
49 |
title |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_unstemmed |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_full |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_fullStr |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_full_unstemmed |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_short |
Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_sort |
production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/akt/ikkα/nf-κb pathway |
topic |
Cell Biology Immunology Immunology and Allergy |
url |
http://dx.doi.org/10.1189/jlb.0904498 |
publishDate |
2005 |
physical |
259-265 |
description |
<jats:title>Abstract</jats:title><jats:p>Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as lipopolysaccharide (LPS) or tumor necrosis factor α and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidylinositol-3 kinase (PI-3K)/Akt/inhibitor of κB (IκB) kinase-α (IKKα)/nuclear factor (NF)-κB pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of PI-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-κB, as shown by coimmunoprecipitation of the phosphorylated form of IKKα and Akt as well as the SH-5 suppression of the dissociation of IκB from NF-κB and the activation of NF-κB p65. The role of NF-κB in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of IκB from NF-κB. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes.</jats:p> |
container_issue |
1 |
container_start_page |
259 |
container_title |
Journal of Leukocyte Biology |
container_volume |
78 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792344359116472322 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T17:06:18.603Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Production+of+matrix+metalloproteinase-9+by+activated+human+monocytes+involves+a+phosphatidylinositol-3+kinase%2FAkt%2FIKK%CE%B1%2FNF-%CE%BAB+pathway&rft.date=2005-03-30&genre=article&issn=1938-3673&volume=78&issue=1&spage=259&epage=265&pages=259-265&jtitle=Journal+of+Leukocyte+Biology&atitle=Production+of+matrix+metalloproteinase-9+by+activated+human+monocytes+involves+a+phosphatidylinositol-3+kinase%2FAkt%2FIKK%CE%B1%2FNF-%CE%BAB+pathway&aulast=Wahl&aufirst=Larry+M&rft_id=info%3Adoi%2F10.1189%2Fjlb.0904498&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792344359116472322 |
author | Lu, Yunbiao, Wahl, Larry M |
author_facet | Lu, Yunbiao, Wahl, Larry M, Lu, Yunbiao, Wahl, Larry M |
author_sort | lu, yunbiao |
container_issue | 1 |
container_start_page | 259 |
container_title | Journal of Leukocyte Biology |
container_volume | 78 |
description | <jats:title>Abstract</jats:title><jats:p>Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as lipopolysaccharide (LPS) or tumor necrosis factor α and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidylinositol-3 kinase (PI-3K)/Akt/inhibitor of κB (IκB) kinase-α (IKKα)/nuclear factor (NF)-κB pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of PI-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-κB, as shown by coimmunoprecipitation of the phosphorylated form of IKKα and Akt as well as the SH-5 suppression of the dissociation of IκB from NF-κB and the activation of NF-κB p65. The role of NF-κB in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of IκB from NF-κB. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes.</jats:p> |
doi_str_mv | 10.1189/jlb.0904498 |
facet_avail | Online, Free |
finc_class_facet | Biologie, Medizin |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4OS9qbGIuMDkwNDQ5OA |
imprint | Oxford University Press (OUP), 2005 |
imprint_str_mv | Oxford University Press (OUP), 2005 |
institution | DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4 |
issn | 0741-5400, 1938-3673 |
issn_str_mv | 0741-5400, 1938-3673 |
language | English |
last_indexed | 2024-03-01T17:06:18.603Z |
match_str | lu2005productionofmatrixmetalloproteinase9byactivatedhumanmonocytesinvolvesaphosphatidylinositol3kinaseaktikkanfkbpathway |
mega_collection | Oxford University Press (OUP) (CrossRef) |
physical | 259-265 |
publishDate | 2005 |
publishDateSort | 2005 |
publisher | Oxford University Press (OUP) |
record_format | ai |
recordtype | ai |
series | Journal of Leukocyte Biology |
source_id | 49 |
spelling | Lu, Yunbiao Wahl, Larry M 0741-5400 1938-3673 Oxford University Press (OUP) Cell Biology Immunology Immunology and Allergy http://dx.doi.org/10.1189/jlb.0904498 <jats:title>Abstract</jats:title><jats:p>Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as lipopolysaccharide (LPS) or tumor necrosis factor α and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidylinositol-3 kinase (PI-3K)/Akt/inhibitor of κB (IκB) kinase-α (IKKα)/nuclear factor (NF)-κB pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of PI-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-κB, as shown by coimmunoprecipitation of the phosphorylated form of IKKα and Akt as well as the SH-5 suppression of the dissociation of IκB from NF-κB and the activation of NF-κB p65. The role of NF-κB in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of IκB from NF-κB. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes.</jats:p> Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway Journal of Leukocyte Biology |
spellingShingle | Lu, Yunbiao, Wahl, Larry M, Journal of Leukocyte Biology, Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway, Cell Biology, Immunology, Immunology and Allergy |
title | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_full | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_fullStr | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_full_unstemmed | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_short | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
title_sort | production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/akt/ikkα/nf-κb pathway |
title_unstemmed | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKα/NF-κB pathway |
topic | Cell Biology, Immunology, Immunology and Allergy |
url | http://dx.doi.org/10.1189/jlb.0904498 |