High IFN-α expression is associated with the induction of experimental autoimmune uveitis (EAU) in Fischer 344 rat
| Autor: | Lei Zang, Yong Jun Hu, Bing Sun, Ya Di Wu |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
medicine.medical_specialty medicine.medical_treatment Biology Pertussis toxin Autoimmune Diseases Pathogenesis Uveitis Interferon-gamma In vivo Internal medicine medicine Macrophage Animals RNA Messenger Virulence Factors Bordetella Lymph node Molecular Biology MHC class II Interferon-alpha Cell Biology Th1 Cells Molecular biology eye diseases In vitro Rats Inbred F344 Rats Endocrinology medicine.anatomical_structure Pertussis Toxin biology.protein Female Adjuvant |
| Zdroj: | Cell Research. 11:293-300 |
| ISSN: | 1748-7838 1001-0602 |
| DOI: | 10.1038/sj.cr.293 |
| Popis: | Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-alpha are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA+R16+PTX-treated (CRP-treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, IFN-gamma mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-alpha mRNA expression were compared in the experimental groups, only IFN-alpha mRNA expression was associated with EAU development. To distinguish the sources of IFN-alpha producing cells, it was observed that IFN-alpha expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-alpha in the presence of PTX. The data strongly suggested that IFN-alpha might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High IFN-alpha expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|