Activated STING enhances Tregs infiltration in the HPV-related carcinogenesis of tongue squamous cells via the c-jun/CCL22 signal.

The negative role of the activated stimulator of IFN genes (STING) has been uncovered in autoinflammatory disease and cancer. However, the role of STING in virus-related carcinogenesis is not well known. Herein, HPV(+) tongue squamous cell carcinoma (TSCC) (n=25) and HPV(-) TSCC samples (n=25) were randomly collected and were verified by in situ hybridization (ISH) and p16 immunohistochemistry (IHC) to assess the expression and activated status of STING through IHC. The results showed that the expression of STING was up-regulated during the development of TSCC. Interestingly, although the expression of STING showed no difference between HPV(+/-) TSCC samples, the activated status of STING with dark staining around the nucleus was observed in HPV(+) TSCC samples. The role of activated STING was analyzed in three cell lines by siRNA and indicated that activated STING had no impact on cell viability or apoptosis but promoted the induction of several immunosuppressive cytokines, e.g., IL-10, IDO and CCL22, which facilitated the infiltration of regulatory T cells (Tregs). Moreover, increased infiltration of Foxp3(+) Tregs along with increased expression of CCL22 was confirmed in HPV(+) TSCC samples. An inhibitor of the MAPK/AP-1 pathway (U0126) and the silencing of c-jun significantly suppressed CCL22 induction and the recruitment of Tregs by activated STING. Furthermore, down-regulated miR-27 was verified in independent fresh TSCC samples (n=50) and eight cell lines, which enhanced STING activation and led to increased CCL22 expression for Tregs recruitment in the TSCC microenvironment. Therefore, our findings provided distinct insight into the side effects of activated STING in HPV-related carcinogenesis.

Aberrant expression of sperm protein 17 enhances migration of ovarian cancer cell line HO-8910 / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the effects of aberrant expression of sperm protein 17 (Sp17) on the migration of the ovarian cancer cell line HO-8910.</p><p><b>METHODS</b>The recombinant plasmid pEGFP-Sp17 containing Sp17 and enhanced green fluorescent protein gene was transfected into the human ovarian cancer cell line HO-8910 with Lipofectamine 2000. The expression of Sp17 was examined by RT-PCR and Western blot, and the cell migratory capability detected by Transwell chamber assays.</p><p><b>RESULTS</b>Sp17 was expressed as a fusion protein with EGFP after transfected. There was a significant difference in the migratory cell number of the transfected and the control cells (156.6 +/- 14.9/HP vs 39.3 +/- 8.53/HP, P < 0.05).</p><p><b>CONCLUSION</b>The aberrant expression of Sp17 greatly enhances the migration of ovarian cancer cells.</p>

Immunoregulatory effects of bone marrow-derived mesenchymal stem cells from NZBWF1/J mice on T lymphocyte subsets balance / 中华风湿病学杂志

Objective To investigate the immunoregulatory effect and compare the different regula- tions of bone marrow mescnchymal stem cells(MSCs)derived from both lupus(NZBWF1/J)and normal(BALB/ c)mice on T lymphocytes in vitro.Methods MSCs from NZBWF1/J and BALB/c mice bone marrow were iso- lated and expanded,and identified by the surface phenotypes.CD3~+ T lymphocytes isolated by nylon wool columns were stimulated by phorbol myristate acetate(PMA)and co-cultured with or without the two strains of MSCs for 24 h.Intracellular eytokines of T cell,such as interferon(IFN)-?,interleukin(IL)-4,IL-12,IL-6, were analyzed by flow cytometry and quantification of transcription factors T-box expressed in T cells(T-bet) and GATA-binding protein 3(GATA-3)were detected by reverse transcriptase PCR(RT-PCR).T cell apop- tosis was assessed by flow cytometry using rhodamine123.Results The results showed that a decrease of CD3~+ T cell apoptosis was seen when NZBWF1/J MSCs or BALB/c MSCs were added to T cells stimulated by PMA(P＜0.05),and an increase of TH2 cytokines by NZBWF1/J MSCs and TH1 eytokines by BALB/c MSCs were observed in the CD3~+ T cells eo-cuhured with MSCs(P＜0.05).Conclusion It is suggested that the al- teration of T subsets caused by MSCs may interfere with the systemic lupus erythematosus(SLE)development and normal MSCs may be effective in the improvement of SLE.NZBWF1/J MSCs have defective immunoregula- tory function when compared with MSCs from healthy mouse strains.

Immunophenotypic characteristics of uterinenatural killer cells and helper T cell 1/ helper T cell 2 immunity in the third trimester decidua of preeclampsia patients / 中华妇产科杂志

Objective To investigate immunophenotypic characteristics of uterine natural killer (uNK)cells and helper T cell 1/helper T cell 2(Th1/Th2)immunity in third trimester decidua in preeclampsia.Methods The proportions of uNK cell subsets,expression of CD_(69)and CD_(94)on uNK cells and Th1/Th2 immunity in decidua were determined in 20 cases of preeclampsia patients and 11 cases of normal term pregnancies by flow cytometric analysis.Results The percentage of CD_(56)~(bright)CD_(16)~-uNK cell subset in preeclampsia patients and the controls was(17.3?11.1)% vs(17.9?16.8)%,that of CD_(56)~(dim) CD_(16)~+uNK cell subset was(16.3?8.7)% vs(16.2?8.8)%;that of CD_(56)~+CD_(69)~+uNK cells was(37.9 ?18.9)% vs(36.8?19.7)%,that of CD_(56)~+CD_(94)~+uNK cells was(34.9?15.2)% vs(32.7?16.2)% and the ratio of CD_(56)~+CD_(69)~+/CD_(56)~+CD_(94)~+was 1.1?0.2,1.2?0.6.No statistical difference was shown in the above values between the preeclampsia patients and controls.The percentage of cytoto xic T cell(Tc)2 cells was significantly lower in the decidua of preeclampsia patients [(3.0?1.0)% vs(4.3?0.9)%,P= 0.001 ],and the ratio of Tc1/Tc2 in preeclampsia patients was significantly higher than that of normal term pregnancies(17.8?3.4 vs 11.8?4.6;P=0.001);the ratio of Th1/Th2 was increased(15.1?2.4 vs 13.2?3.1;P=0.06).Conclusions The immunophenotypie characteristics of uNK cells do not present any significant change in preeclampsia patients.Owing to Tc2 cell decrease,the Th1/Th2 immunity shifts to Th1 type immunity in the decidua,which might contribute to the pathogenesis of preeclampsia.