Downregulation of interleukin-7 and hepatocyte growth factor in the thymic microenvironment is associated with thymus involution in tumor-bearing mice |
| |
Authors: | Roberto Carrio Norman H Altman Diana M Lopez |
| |
Institution: | (1) Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, P.O. Box 016960, Miami, FL 33101, USA;(2) Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; |
| |
Abstract: | During mammary tumorigenesis, there is a profound thymic involution associated with severe depletion of the most abundant
subset of thymocytes, CD4+CD8+ immature cells, and an early arrest in at least two steps of T cell differentiation. Thymic atrophy that is normally related
with aging has been observed in other model systems, including graft-vs-host disease (GVHD) and tumor development. However,
the mechanisms involved in this phenomenon remain to be elucidated. Vascular endothelial growth factor (VEGF) has been associated
with thymic involution, when expressed at high levels systemically. In thymuses of D1-DMBA-3 tumor-bearing mice, this growth
factor is diminished relative to the level of normal thymuses. Interestingly, the expression of hepatocyte growth factor (HGF),
which has been associated with proliferation, cell survival, angiogenesis and B-cell differentiation, is profoundly down-regulated
in thymuses of tumor bearers. In parallel, IL-7 and IL-15 mRNA, crucial cytokines involved in thymocytes development and cellular
homeostasis, respectively, are also down-regulated in the thymuses of tumor hosts as compared to those of normal mice. Injection
of HGF into mice implanted with mammary tumors resulted in normalization of thymic volume and levels of VEGF, IL-7 and IL-15.
While, injections of IL-7 partially restored the thymic involution observed in the thymuses of tumor-bearing mice, injection
of IL-15 did not have any significant effects. Our data suggest that the downregulation of HGF and IL-7 may play an important
role in the thymic involution observed in tumor-bearing hosts. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|