Exp Mol Med.
2008 Feb;40(1):59-70. 10.3858/emm.2008.40.1.59.
RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells
- Affiliations
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- 1Department of Anatomy, School of Medicine, Pusan National University, Busan 602-739, Korea. sikyoon@pusan.ac.kr
- 2Department of Obstetrics and Gynecology, School of Medicine, Pusan National University, Busan 602-739, Korea.
- 3Department of Pharmacology, School of Medicine, Pusan National University, Busan 602-739, Korea.
- 4Medical Research Institute, School of Medicine, Pusan National University, Busan 602-739, Korea.
- 5Division of Rheumatology, Wallace Memorial Baptist Hospital, Busan 609-728, Korea.
- 6College of Pharmacy, Pusan National University, Busan 609-735, Korea.
- 7Medical Research Center for Ischemic Tissue Regeneration, Korea.
- 8Pusan National University Medical Science Education Center (BK21 Program), School of Medicine, Pusan National University, School of Medicine, Pusan National University, Busan 602-739, Korea.
- 99Department of Ophthalmology, Busan Medical Center, Busan 611-072, Korea.
- KMID: 1103589
- DOI: http://doi.org/10.3858/emm.2008.40.1.59
Abstract
- Abstract In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-kappaB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.
MeSH Terms
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Animals
Cell Adhesion/drug effects
Cell Line
Cell Proliferation/drug effects
Cyclophosphamide/pharmacology
Down-Regulation/drug effects
Epithelial Cells/*cytology/drug effects/*metabolism
Granulocyte-Macrophage Colony-Stimulating Factor/genetics/metabolism
Intercellular Adhesion Molecule-1/genetics/metabolism
Interleukin-7/*genetics/*metabolism
Male
Mice
Mice, Inbred C57BL
RANK Ligand/*pharmacology
RNA, Messenger/genetics/metabolism
Receptor Activator of Nuclear Factor-kappa B/genetics/metabolism
Regeneration/drug effects
Thymus Gland/*cytology/*drug effects/physiology
Up-Regulation/drug effects
Vascular Cell Adhesion Molecule-1/genetics/metabolism
bcl-2-Associated X Protein/genetics/metabolism
bcl-X Protein/genetics/metabolism
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