NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts
The transcription factor NF-κB is of major importance in the biology of pro-inflammatory cytokines, such as TNF-α and IL-1α, and thereby is intimately involved in the process of inflammation. Understanding the mechanisms by which NF-κB is activated in response to inflammatory stimuli has become a ma...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2001
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| _version_ | 1826306307403022336 |
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| author | Smith, C Andreakos, E Crawley, J Brennan, F Feldmann, M Foxwell, B |
| author_facet | Smith, C Andreakos, E Crawley, J Brennan, F Feldmann, M Foxwell, B |
| author_sort | Smith, C |
| collection | OXFORD |
| description | The transcription factor NF-κB is of major importance in the biology of pro-inflammatory cytokines, such as TNF-α and IL-1α, and thereby is intimately involved in the process of inflammation. Understanding the mechanisms by which NF-κB is activated in response to inflammatory stimuli has become a major goal of inflammation research. The discovery of NF-κB-inducing kinase (NIK) as a TNFR-associated factor-interacting enzyme and a potential activator of the IκBα-kinase complex appeared to have identified an important element of the NF-κB activition pathway, a view that was supported by several subsequent studies. However, recent experiments in the alymphoplasia (aly/aly) mouse, which has missense point mutation (G885R) in NIK, has challenged that view. The reasons for the discrepancy between the different studies is unclear and could be due to multiple factors, such as cell type, species of cell, or primary vs transformed cell lines. One system that has not been investigated is primary human cells. Using an adenoviral vector encoding kinase-deficient NIK, we have investigated the role of NIK in LPS, IL-1, TNF-α, and lymphotoxin (LT) βR signaling in primary human cells and TNF-α expression from rheumatoid tissue. These data show that, in the primary systems tested, NIK has a restricted role in LTβR signaling and is not required by the other stimuli tested. Also, there is no apparent role for NIK in the process of TNF-α production in human rheumatoid arthritis. These data also highlight the potential problems in extrapolating the function of signaling pathways between primary and transfected cell lines. |
| first_indexed | 2024-03-07T06:45:58Z |
| format | Journal article |
| id | oxford-uuid:fadd6e16-8683-4f30-8375-1c597d4127e1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:45:58Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:fadd6e16-8683-4f30-8375-1c597d4127e12022-03-27T13:09:26ZNF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblastsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fadd6e16-8683-4f30-8375-1c597d4127e1EnglishSymplectic Elements at Oxford2001Smith, CAndreakos, ECrawley, JBrennan, FFeldmann, MFoxwell, BThe transcription factor NF-κB is of major importance in the biology of pro-inflammatory cytokines, such as TNF-α and IL-1α, and thereby is intimately involved in the process of inflammation. Understanding the mechanisms by which NF-κB is activated in response to inflammatory stimuli has become a major goal of inflammation research. The discovery of NF-κB-inducing kinase (NIK) as a TNFR-associated factor-interacting enzyme and a potential activator of the IκBα-kinase complex appeared to have identified an important element of the NF-κB activition pathway, a view that was supported by several subsequent studies. However, recent experiments in the alymphoplasia (aly/aly) mouse, which has missense point mutation (G885R) in NIK, has challenged that view. The reasons for the discrepancy between the different studies is unclear and could be due to multiple factors, such as cell type, species of cell, or primary vs transformed cell lines. One system that has not been investigated is primary human cells. Using an adenoviral vector encoding kinase-deficient NIK, we have investigated the role of NIK in LPS, IL-1, TNF-α, and lymphotoxin (LT) βR signaling in primary human cells and TNF-α expression from rheumatoid tissue. These data show that, in the primary systems tested, NIK has a restricted role in LTβR signaling and is not required by the other stimuli tested. Also, there is no apparent role for NIK in the process of TNF-α production in human rheumatoid arthritis. These data also highlight the potential problems in extrapolating the function of signaling pathways between primary and transfected cell lines. |
| spellingShingle | Smith, C Andreakos, E Crawley, J Brennan, F Feldmann, M Foxwell, B NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title | NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title_full | NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title_fullStr | NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title_full_unstemmed | NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title_short | NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts |
| title_sort | nf κb inducing kinase is dispensable for activation of nf κb in inflammatory settings but essential for lymphotoxin β receptor activation of nf κb in primary human fibroblasts |
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