Varying IL-6 concentration initiates qualitatively distinct signaling responses and genetic programs
Abstract/Contents
- Abstract
- IL-6 is a pleiotropic cytokine with roles in many areas of biology; it is also implicated in diseases associated with inflammation. To understand how a molecule is capable of diverse effects, one must understand how cells respond to it. In most published studies, the mechanism of IL-6 signaling has been evaluated in cell lines with limited biological relevance. In this study, phospho-specific flow cytometry and other techniques were used to look closely at IL-6 signaling in primary murine lymphocytes. Splenic T cells, but not B cells, exhibited a strong phospho-STAT1 response to IL-6 in addition to the universally observed STAT3 activation. Interestingly, when IL-6 dose was reduced, T cells exhibited a B cell-like signaling phenotype; they had no phospho-STAT1 response to IL-6. STAT3 had a greater affinity than STAT1 for gp130, the IL-6 signal transducer, which allows STAT3 to become activated when IL-6 is scarce. In our system, STAT1 played a dual role in gene transcription downstream of IL-6. In contrast with previous reports, phospho-STAT1 was required for expression of a subset of genes, which indicates that nature has the ability to create a STAT1 knockout-like condition by stimulating cells with a low level of IL-6. A novel inhibitory function of STAT1, which indicates a modality used to influence TH biasing capability of IL-6, was also discovered. This work gives insight as to how a single molecule, IL-6, affects the immune system, the central nervous system, and metabolism in such complex ways.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Schulz, Kenneth Randal |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Nolan, Garry P |
| Thesis advisor | Nolan, Garry P |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Levy, Ronald, 1941 December 6- |
| Thesis advisor | Utz, Paul |
| Advisor | Davis, Mark M |
| Advisor | Levy, Ronald, 1941 December 6- |
| Advisor | Utz, Paul |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Kenneth Randal Schulz. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Kenneth Randal Schulz
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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