A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs
The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood. It is known that IL-6 induces a transient STAT3 signal and that IL-10 induces a sustained STAT3...
| Main Authors: | , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/71783 https://orcid.org/0000-0003-1268-9602 |
| _version_ | 1826194416916758528 |
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| author | Fowler, Kevin Daniel Kuchroo, Vijay K. Chakraborty, Arup K. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Fowler, Kevin Daniel Kuchroo, Vijay K. Chakraborty, Arup K. |
| author_sort | Fowler, Kevin Daniel |
| collection | MIT |
| description | The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood. It is known that IL-6 induces a transient STAT3 signal and that IL-10 induces a sustained STAT3 signal due to the STAT3-induced inhibitor SOCS3's ability to bind to the IL-6R and not the IL-10R. We sought to develop a general transcriptional network that is capable of translating sustained signals into one response, while translating transient signals into a second response. The general structure of such a network is that the transcription factor STAT3 can induce both an inflammatory response and an anti-inflammatory response by inducing two different genes. The anti-inflammatory gene can bind to and inhibit the inflammatory gene's production and the inflammatory gene can bind to its own promoter and induce its own transcription in the absence of the signal. One prediction that can be made from such a network is that in SOCS3−/− mice, where IL-6 induces a sustained STAT3 signal, that IL-6 would act as an anti-inflammatory cytokine, which has indeed been observed experimentally in the literature. |
| first_indexed | 2024-09-23T09:55:46Z |
| format | Article |
| id | mit-1721.1/71783 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:55:46Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/717832022-09-30T17:45:36Z A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs Fowler, Kevin Daniel Kuchroo, Vijay K. Chakraborty, Arup K. Massachusetts Institute of Technology. Department of Chemical Engineering Chakraborty, Arup K. Fowler, Kevin Daniel Chakraborty, Arup K. The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood. It is known that IL-6 induces a transient STAT3 signal and that IL-10 induces a sustained STAT3 signal due to the STAT3-induced inhibitor SOCS3's ability to bind to the IL-6R and not the IL-10R. We sought to develop a general transcriptional network that is capable of translating sustained signals into one response, while translating transient signals into a second response. The general structure of such a network is that the transcription factor STAT3 can induce both an inflammatory response and an anti-inflammatory response by inducing two different genes. The anti-inflammatory gene can bind to and inhibit the inflammatory gene's production and the inflammatory gene can bind to its own promoter and induce its own transcription in the absence of the signal. One prediction that can be made from such a network is that in SOCS3−/− mice, where IL-6 induces a sustained STAT3 signal, that IL-6 would act as an anti-inflammatory cytokine, which has indeed been observed experimentally in the literature. National Institutes of Health (U.S.). Director's Pioneer Award 2012-07-24T16:25:25Z 2012-07-24T16:25:25Z 2012-03 2011-11 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/71783 Fowler, Kevin D., Vijay K. Kuchroo, and Arup K. Chakraborty. “A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs.” Ed. Laurel L. Lenz. PLoS ONE 7.3 (2012): e33018. https://orcid.org/0000-0003-1268-9602 en_US http://dx.doi.org/10.1371/journal.pone.0033018 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Fowler, Kevin Daniel Kuchroo, Vijay K. Chakraborty, Arup K. A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title | A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title_full | A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title_fullStr | A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title_full_unstemmed | A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title_short | A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs |
| title_sort | model for how signal duration can determine distinct outcomes of gene transcription programs |
| url | http://hdl.handle.net/1721.1/71783 https://orcid.org/0000-0003-1268-9602 |
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