Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo
The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome character...
| Main Authors: | , , , , , , , , , , , |
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| 格式: | Journal article |
| 语言: | English |
| 出版: |
American Society for Microbiology
2017
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| _version_ | 1826276502386245632 |
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| author | O'Neil, JD Ross, EA Ridley, ML Ding, Q Tang, T Rosner, DR Crowley, T Malhi, D Dean, JL Smallie, T Buckley, CD Clark, AR |
| author_facet | O'Neil, JD Ross, EA Ridley, ML Ding, Q Tang, T Rosner, DR Crowley, T Malhi, D Dean, JL Smallie, T Buckley, CD Clark, AR |
| author_sort | O'Neil, JD |
| collection | OXFORD |
| description | The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino acids of the endogenous TTP protein renders it constitutively active as an mRNA-destabilizing factor. Here we investigate the impact on the IL-10-mediated anti-inflammatory response. It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated negative feedback control of macrophage function in vitro However, the in vivo effects of TTP mutation are uniformly anti-inflammatory despite the decreased expression of IL-10. |
| first_indexed | 2024-03-06T23:14:55Z |
| format | Journal article |
| id | oxford-uuid:66cd83d2-e49f-4e2d-b7f3-7425e65d84f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:14:55Z |
| publishDate | 2017 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:66cd83d2-e49f-4e2d-b7f3-7425e65d84f42022-03-26T18:34:11ZGain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivoJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:66cd83d2-e49f-4e2d-b7f3-7425e65d84f4EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2017O'Neil, JDRoss, EARidley, MLDing, QTang, TRosner, DRCrowley, TMalhi, DDean, JLSmallie, TBuckley, CDClark, ARThe mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino acids of the endogenous TTP protein renders it constitutively active as an mRNA-destabilizing factor. Here we investigate the impact on the IL-10-mediated anti-inflammatory response. It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated negative feedback control of macrophage function in vitro However, the in vivo effects of TTP mutation are uniformly anti-inflammatory despite the decreased expression of IL-10. |
| spellingShingle | O'Neil, JD Ross, EA Ridley, ML Ding, Q Tang, T Rosner, DR Crowley, T Malhi, D Dean, JL Smallie, T Buckley, CD Clark, AR Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title | Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title_full | Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title_fullStr | Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title_full_unstemmed | Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title_short | Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo |
| title_sort | gain of function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti inflammatory consequences in vivo |
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