The role of epidermal growth factor receptor in autoimmune arthritis
Abstract/Contents
- Abstract
- Rheumatoid arthritis (RA) is an autoimmune synovitis affecting approximately 0.5% of the population worldwide. In addition to T cells, B cells and macrophages, cells such as synovial fibroblasts promote inflammation in the synovium by producing cytokines and chemokines. At the same time, neovascularization provides nutrients and oxygen to the growing pannus and increased osteoclastogenesis causes bone destruction. RA serum and synovial fluid contains increased concentrations of epidermal growth factor receptor (EGFR) ligands; and synovial fibroblasts and endothelial cells in RA synovium express EGFR. Thus, we hypothesized that a specific EGFR tyrosine kinase inhibitor, erlotinib, would ameliorate murine collagen-induced arthritis (CIA). Erlotinib is currently prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. Here, we demonstrate that erlotinib reduces the severity of established murine CIA and investigated the mechanisms of this inhibition. Erlotinib reduced: 1) EGF-induced proliferation of fibroblasts and human umbilical vein endothelial cells (HUVEC), 2) EGF-induced production of IL-8 and vascular endothelial cell growth factor (VEGF) by fibroblasts, and 3) the development of osteoclasts from bone marrow cells. Together, these findings suggest that EGFR plays a central role in the pathogenesis of RA and that EGFR inhibition may provide benefit in the treatment of RA.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Swanson, Christina D'Aura | |
|---|---|---|
| Associated with | Stanford University, Program in Immunology. | |
| Primary advisor | Robinson, William (William Hewitt) | |
| Thesis advisor | Robinson, William (William Hewitt) | |
| Thesis advisor | Fathman, C. Garrison | |
| Thesis advisor | Sobel, Raymond (Raymond A.) | |
| Thesis advisor | Steinman, Lawrence | |
| Advisor | Fathman, C. Garrison | |
| Advisor | Sobel, Raymond (Raymond A.) | |
| Advisor | Steinman, Lawrence |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Christina D'Aura Swanson. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Christina D'Aura Swanson
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