The Epistatic Interrelationships of IL-1, IL-1 Receptor Antagonist, and the Type I IL-1 Receptor
| Autor: | Mouna Lagraoui, Vera M. Irikura, David Hirsh |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.drug_class
Sialoglycoproteins Immunology Mice Transgenic In Vitro Techniques Biology Proinflammatory cytokine Mice Immune system medicine Animals Homeostasis Immunology and Allergy Listeriosis Receptor Gene Crosses Genetic Growth Disorders Inflammation Mice Knockout Genetics Antagonist Receptors Interleukin-1 Epistasis Genetic Receptor antagonist Shock Septic Survival Analysis Cell biology Mice Inbred C57BL Interleukin 1 Receptor Antagonist Protein Animals Newborn Interleukin-21 receptor Cytokines Female Interleukin-1 |
| Zdroj: | The Journal of Immunology. 169:393-398 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.1.393 |
| Popis: | Mice lacking the gene for the IL-1R antagonist (IL-1ra) show abnormal development and homeostasis as well as altered responses to infectious and inflammatory stimuli. A reduction in the level of IL-1 signaling, either by deletion of the receptor or increased expression of IL-1ra, does not affect development or homeostasis, but does alter immune responses. In this study we use genetic epistasis to investigate the interdependence of selected genes in the IL-1 family in the regulation of these developmental and immunological processes. Deletion of the gene encoding the type I IL-1R (IL-1RI) is epistatic to deletion of the IL-1ra gene. Therefore, all functions of IL-1ra depend upon the presence of a functional receptor; there is no other target. Similarly, overexpression of the mRNA encoding the secreted form of IL-1ra is epistatic to deletion of the receptor antagonist, leaving the role of the intracellular splice variants of IL-1ra unknown. The abnormal development of IL-1ra-deficient mice is probably due to chronic overstimulation of the proinflammatory pathway via IL-1, but a clear single pathological defect is not apparent. These results support the model that the only essential function of IL-1ra in both health and disease is competitive inhibition of the IL-1RI. |
| Databáze: | OpenAIRE |
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