RESUMO
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.
Assuntos
Animais , Masculino , Camundongos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclofosfamida/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-7/genética , Camundongos Endogâmicos C57BL , Ligante RANK/farmacologia , RNA Mensageiro/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Regeneração/efeitos dos fármacos , Timo/citologia , Regulação para Cima/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/genética , Proteína X Associada a bcl-2/genética , Proteína bcl-X/genéticaRESUMO
OBJECTIVE To study the content and distribution characteristics of thymic stromal lymphopoietin (TSLP) in nasal mucosa of murine model of allergic rhinitis.METHODS 6-week-old BALB/c mice were divided into control group and experimental group.Mice of experimental group were sensitized by means of dropping OVA in nasal cavity and intraperitoneal injection of OVA. Meanwhile,mice of control group were dealt with physiological saline instead of OVA.The content of TSLP in nasal mucosa of mice was tested by means of real-time PCR and its distribution was detected by means of immunohistochemistry staining.RESULTS The content of TSLP was obviously higher in nasal mucosa of experimental group than that of control group.It was distributed mainly in lamina propria and on the surface of epithelium.CONCLUSION TSLP may play an important role in allergic rhinitis of the mice.
RESUMO
TP5 and CsA were injected-intraperitoneally into groups of experimental mice, and NS was used for the contral group. Herpes simplex keratitis models were made subsequently by inoculation of the virus on the cornea. On the 4～6th day after inoculation, slit lamp examination showed that the corneal epithelial and stromal lesions in the TP5 group were significantly more severe than those in the NS group, whereas the group of CsA manifested no such differences. Among the 3 groups of mice, no differences were evident in the formation of corneal neovascularization, which all peaked on the 8th day. The conjuctival and palpebral lesions in the TP5 and CsA groups were also more severe than in NS group. Therefore, immunomodulators should be clinically used with care in accordance with the morbid varieties and conditions.