We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human N...We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.展开更多
Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of in...Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD： TNF- 308A, CARD15 （NOD2）, MIF-173, N-acetyltransferase 2 （NAT2）, NKG2D （natural killer cell 2D）, STAT6 （signal transducer and activator of transcription 6）, CTLA-4 （cytotoxic T lymphocyte antigen-4）, MICA-MICB （major histocompatibility complex A and B）, HLA-DRB1, HLA class-Ⅱ, IL-18, IL-4, MICA-A5, CD14, TI R4, Fas-670, p53 and NF-kB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD （UC and CD）.展开更多
基金supported partly by Outstanding Young Scientist Award and Key Project by Natural Science Foundation of China(No.30125038,No.30230340)The Major Sate Basic research Development program of China(No.2001CB510009)+1 种基金The National high technology research and Development program of China(No.2002AA216151)by Ministry of Science and Technology of ChinaKey Project by Chinese Academy of Science(No.KSCX2-2-08).
文摘We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.
基金Supported by The Science Foundation of Health Bureau of Shaanxi Province,China,No.04D26
文摘Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD： TNF- 308A, CARD15 （NOD2）, MIF-173, N-acetyltransferase 2 （NAT2）, NKG2D （natural killer cell 2D）, STAT6 （signal transducer and activator of transcription 6）, CTLA-4 （cytotoxic T lymphocyte antigen-4）, MICA-MICB （major histocompatibility complex A and B）, HLA-DRB1, HLA class-Ⅱ, IL-18, IL-4, MICA-A5, CD14, TI R4, Fas-670, p53 and NF-kB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD （UC and CD）.
