Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse
| Autor: | Lucia Gabriele, R.A. Morawetz, Keiko Ozato, N.A. Giese, Herbert C. Morse, P. Rothman, I. Horak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Physiology
medicine.medical_treatment Immunology Biophysics Disease ICSBP Biochemistry Mice Retrovirus MAIDS Interferon Murine Acquired Immunodeficiency Syndrome medicine Animals General Pharmacology Toxicology and Pharmaceutics Receptors Cytokine lcsh:QH301-705.5 Immunodeficiency lcsh:R5-920 biology General Neuroscience Cell Biology General Medicine interferon medicine.disease biology.organism_classification Haematopoiesis Disease Models Animal Cytokine lcsh:Biology (General) Cytokines Signal transduction lcsh:Medicine (General) immunodeficiency Chronic myelogenous leukemia medicine.drug Retroviridae Infections |
| Zdroj: | Brazilian Journal of Medical and Biological Research, Volume: 31, Issue: 1, Pages: 61-67, Published: JAN 1998 Brazilian Journal of Medical and Biological Research, Vol 31, Iss 1, Pp 61-67 (1998) Scopus-Elsevier Brazilian Journal of Medical and Biological Research v.31 n.1 1998 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
| Popis: | The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs |
| Databáze: | OpenAIRE |
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