Ragweed pollen induces allergic conjunctivitis immune tolerance in mice via regulation of the NF-κB signal pathway

AIM:To investigate the feasibility and mechanism of immune tolerance in allergic conjunctivitis.METHODS:The allergic conjunctivitis immune tolerance mice model was established by ragweed pollen(RW)and the related cytokines were detected.The mice were divided into 9 groups and the maslinic acid(MA)or PBS were given for different group after modeling.The expression levels of chemokine ligand 5(CCL5)and P-65 in the conjunctival tissue were analyzed by immunohistochemistry,quantitative reverse transcription polymerase chain reaction(q RT-PCR)and Western blot.The percentage of interleukin-17(IL-17)and CD4+CD25+in the splenocyte supernatant was analyzed by flow cytometry.Fur thermore,the serum and splenocyte supernatant concentration of total-IgE,interleukin-10(IL-10),and IL-17 was analyzed by enzyme linked immune response(ELISA).RESULTS:After the model was established,symptoms of conjunctivitis were alleviated,the level of P-65,CCL5,IL-17,and total-IgE was raised,while the expression of IL-10,CD4+CD25+was decreased.This result fully demonstrated that a typical IL-17/regulatory-T-cells(Treg cells)imbalance and NF-κB activation.When the NF-κB signal pathway was suppressed,it showed that there was a further relief of conjunctivitis in mice.At the same time,the expression of total-IgE,IL-17,and CCL5 was decreased and the expression of anti-inflammatory factor(IL-10,CD4+CD25+)was increased.CONCLUSION:In the state of immune tolerance,symptoms of conjunctivitis in mice are alleviated,the Th-17 cells of allergic conjunctivitis mice are inhibited,and Treg cells activity is enhanced.

Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB/IL-6/STAT3 and JNK/PTX3 pathways

Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.