Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent.
OBJECTIVE: To determine whether, in human fibroblasts and chondrosarcoma cells, the regulation of interleukins (IL)-6, 8, and 11 and matrix metalloproteinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappaB (NF-kappaB). METHODS: Fibrob...
Main Authors: | , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2000
|
_version_ | 1797072522938679296 |
---|---|
author | Bondeson, J Brennan, F Foxwell, B Feldmann, M |
author_facet | Bondeson, J Brennan, F Foxwell, B Feldmann, M |
author_sort | Bondeson, J |
collection | OXFORD |
description | OBJECTIVE: To determine whether, in human fibroblasts and chondrosarcoma cells, the regulation of interleukins (IL)-6, 8, and 11 and matrix metalloproteinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappaB (NF-kappaB). METHODS: Fibroblasts and chondrosarcoma cells were effectively infected with an adenovirus encoding human IkappaBalpha, and inhibition of NF-kappaB function was observed. The induction of MMP and IL-6, 8, and 11 by various stimuli was assessed by ELISA. RESULTS: The induction of IL-6 and IL-8 clearly depended on NF-kappaB in both fibroblasts and chondrosarcoma cells, irrespective of stimulus, but IkappaBalpha overexpression had little effect on IL-11. MMP-1, -3, and -13 were also inhibited, but TIMP-1 was unaffected. CONCLUSION: NF-kappaB appears to play an important and selective role in MMP induction in human fibroblasts and chondrosarcoma cells. This suggests there are NF-kappaB dependent mechanisms of cartilage destruction in rheumatoid arthritis, and supports the concept that there are similarities in the regulation of inflammatory and destructive pathways in that disease. |
first_indexed | 2024-03-06T23:08:55Z |
format | Journal article |
id | oxford-uuid:64ccc677-1d53-4f01-9395-7729bde672a9 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T23:08:55Z |
publishDate | 2000 |
record_format | dspace |
spelling | oxford-uuid:64ccc677-1d53-4f01-9395-7729bde672a92022-03-26T18:21:14ZEffective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:64ccc677-1d53-4f01-9395-7729bde672a9EnglishSymplectic Elements at Oxford2000Bondeson, JBrennan, FFoxwell, BFeldmann, MOBJECTIVE: To determine whether, in human fibroblasts and chondrosarcoma cells, the regulation of interleukins (IL)-6, 8, and 11 and matrix metalloproteinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappaB (NF-kappaB). METHODS: Fibroblasts and chondrosarcoma cells were effectively infected with an adenovirus encoding human IkappaBalpha, and inhibition of NF-kappaB function was observed. The induction of MMP and IL-6, 8, and 11 by various stimuli was assessed by ELISA. RESULTS: The induction of IL-6 and IL-8 clearly depended on NF-kappaB in both fibroblasts and chondrosarcoma cells, irrespective of stimulus, but IkappaBalpha overexpression had little effect on IL-11. MMP-1, -3, and -13 were also inhibited, but TIMP-1 was unaffected. CONCLUSION: NF-kappaB appears to play an important and selective role in MMP induction in human fibroblasts and chondrosarcoma cells. This suggests there are NF-kappaB dependent mechanisms of cartilage destruction in rheumatoid arthritis, and supports the concept that there are similarities in the regulation of inflammatory and destructive pathways in that disease. |
spellingShingle | Bondeson, J Brennan, F Foxwell, B Feldmann, M Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title | Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title_full | Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title_fullStr | Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title_full_unstemmed | Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title_short | Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent. |
title_sort | effective adenoviral transfer of ikappabalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor kappab dependent |
work_keys_str_mv | AT bondesonj effectiveadenoviraltransferofikappabalphaintohumanfibroblastsandchondrosarcomacellsrevealsthattheinductionofmatrixmetalloproteinasesandproinflammatorycytokinesisnuclearfactorkappabdependent AT brennanf effectiveadenoviraltransferofikappabalphaintohumanfibroblastsandchondrosarcomacellsrevealsthattheinductionofmatrixmetalloproteinasesandproinflammatorycytokinesisnuclearfactorkappabdependent AT foxwellb effectiveadenoviraltransferofikappabalphaintohumanfibroblastsandchondrosarcomacellsrevealsthattheinductionofmatrixmetalloproteinasesandproinflammatorycytokinesisnuclearfactorkappabdependent AT feldmannm effectiveadenoviraltransferofikappabalphaintohumanfibroblastsandchondrosarcomacellsrevealsthattheinductionofmatrixmetalloproteinasesandproinflammatorycytokinesisnuclearfactorkappabdependent |