In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51...In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51Cr release assay. The enhancement of NK activity with 24 hours preincubation in HrlL-6 was dose-dependent, and significantly higher than that of fresh NK cells and controls cultured with RPMI-1640 medium alone (P<0.001). We also found that IL-6 was able to augment NK activity from different fetal spleens at 20 to 40 weeks of gestation (up to 2.24 to 2.78 times), and no difference of NK activity of fetal splenocytes treated by HrIL-6 was observed between different fetal age (32.3% to 45.4%, P>0.05). Furthermore, IL-6-augmented NK activity of fetal splenocytes was very similar to adult levels (P>0.05). These finding strongly indicated that IL-6 plays an important role in the development of NK cell function during the gestational period, suggesting that IL-6 may be of importance in the regulation of host defense mechanisms against malignancies and viral diseases.展开更多
The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquite...The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E.globulus were immunosuppressive active constituents,especially Eucalyptin C(EuC).Phosphoinositide 3-kinases-γ(PI3Kγ)plays a pivotal role in T cell mediated excessive immune responses.In this study,EuC was first discovered to be a novel selective PI3Kγinhibitor with an IC50 value of 0.9μmol·L^(−1) and selectivity over 40-fold towards the other PI3K isoforms.Molecular docking,molecular dynamics simulation,and cellular thermal shift assay showed that EuC bound to PI3Kγ.Furthermore,EuC suppressed the downstream of PI3Kγto induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice.This work highlights the role of the fruits of E.globulus as a source of bioactive plant with immunosuppressive activity.展开更多
文摘In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51Cr release assay. The enhancement of NK activity with 24 hours preincubation in HrlL-6 was dose-dependent, and significantly higher than that of fresh NK cells and controls cultured with RPMI-1640 medium alone (P<0.001). We also found that IL-6 was able to augment NK activity from different fetal spleens at 20 to 40 weeks of gestation (up to 2.24 to 2.78 times), and no difference of NK activity of fetal splenocytes treated by HrIL-6 was observed between different fetal age (32.3% to 45.4%, P>0.05). Furthermore, IL-6-augmented NK activity of fetal splenocytes was very similar to adult levels (P>0.05). These finding strongly indicated that IL-6 plays an important role in the development of NK cell function during the gestational period, suggesting that IL-6 may be of importance in the regulation of host defense mechanisms against malignancies and viral diseases.
基金This work was supported by China Postdoctoral Science Foundation(Nos.2019M662006 and 2019TQ0357)the National Natural Science Foundation of China(Nos.81973206,81803392 and 81573309)+5 种基金the Major National Science and Technology Projects of the Chinese Thirteen Five-Year Plan(No.2017ZX09309024)the Funding of Double First-rate Discipline Innovation Team(Nos.CPU2018PZQ17,CPU2018PZQ18,and CPU2018GF05)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Research and Innovation Project for College Graduates of Jiangsu Province 2017(No.KYCX170694)the National College Student Innovation Project for the R&D of Novel Drugs(No.201710316100)Jiangsu Province Graduate Student Training Innovation Project(No.KYLX16_1208).
文摘The fruits of Eucalyptus globulus Labill.are known to have a plenty of medicinal properties,such as anti-tumor,anti-inflammatory,and immunosuppressive activity.Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E.globulus were immunosuppressive active constituents,especially Eucalyptin C(EuC).Phosphoinositide 3-kinases-γ(PI3Kγ)plays a pivotal role in T cell mediated excessive immune responses.In this study,EuC was first discovered to be a novel selective PI3Kγinhibitor with an IC50 value of 0.9μmol·L^(−1) and selectivity over 40-fold towards the other PI3K isoforms.Molecular docking,molecular dynamics simulation,and cellular thermal shift assay showed that EuC bound to PI3Kγ.Furthermore,EuC suppressed the downstream of PI3Kγto induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice.This work highlights the role of the fruits of E.globulus as a source of bioactive plant with immunosuppressive activity.
