Objective： To investigate the effects of CD137 signaling on the regulation of CD3-CD56＋NK cells function. Methods： CD3 CD56＋NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects ...Objective： To investigate the effects of CD137 signaling on the regulation of CD3-CD56＋NK cells function. Methods： CD3 CD56＋NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects of CD 137 signaling on the function of CD3-CD56＋NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-I expression on CD3-CD56＋NK cells were analyzed by flow cytometry. Results： CD137 was expressed on activated CD3-CD56＋NK cells. The CD137 mAb enhanced the ability of CDB-CD56＋NK cells to kill lung cancer cells（A549）; Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells, and blockade of NKG2D and LFA-1 dramatically attenuated CD3CD56＋NK cytolysis of A549 cancer cells. Conclusion： CD 137 signaling increases the ability of CD3-CD56＋NK cells to kill cancer cells via up- regulating the expression of NKG2D and LFA-1.展开更多
Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase （JNK） participates in the apoptosis of retinal ganglion cells in...Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase （JNK） participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by pho- tocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.展开更多
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2...The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD） （HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.展开更多
基金supported by National Nature Science Foundation of China (No.30772549)
文摘Objective： To investigate the effects of CD137 signaling on the regulation of CD3-CD56＋NK cells function. Methods： CD3 CD56＋NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects of CD 137 signaling on the function of CD3-CD56＋NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-I expression on CD3-CD56＋NK cells were analyzed by flow cytometry. Results： CD137 was expressed on activated CD3-CD56＋NK cells. The CD137 mAb enhanced the ability of CDB-CD56＋NK cells to kill lung cancer cells（A549）; Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells, and blockade of NKG2D and LFA-1 dramatically attenuated CD3CD56＋NK cytolysis of A549 cancer cells. Conclusion： CD 137 signaling increases the ability of CD3-CD56＋NK cells to kill cancer cells via up- regulating the expression of NKG2D and LFA-1.
基金supported by grants from the Youth Foundation of Luzhou Medical College of Luzhou City of Sichuan Province of China,No.[2010]108the Talent Fund of the Affiliated Hospital of Luzhou Medical College of Luzhou City of Sichuan Province of China,No.[2011]43
文摘Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase （JNK） participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by pho- tocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.
基金supported by the National Natural Science Foundation of China (81270644, 81670166, 81230013, 81530046)the Beijing Talents fund (2015000021223ZK26)+2 种基金the Major State Basic Research Development Program of China (2013CB733700)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001)supported by the Collaborative Innovation Center of Hematology, China
文摘The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD） （HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.
