Interferon regulatory factor-4 binding protein (IBP) is a novel upstream activator of Rho GTPases. Our previous studies have shown that ectopic expression of IBP was correlated with malignant behaviors of human breast cancer cells, and invasive human breast cancer had high expression of IBP that promoted the proliferation of these cells. However, it remains unknown whether autophagy inhibition contributes to IBP-mediated tumorigenesis. In this study, we for the first time, reported that upregulation of IBP expression significantly suppressed the autophagy of breast cancer cells, and downregulation of IBP expression markedly induced autophagy of these cells. Further investigation revealed that IBP effectively counteracted autophagy by directly activating mammalian target of rapamycin complex 2 (mTORC2) and upregulating phosphorylation of Akt on ser473 and FOXO3a on Thr32. Moreover, IBP-mediated suppression of autophagy was dependent on mTORC2/Akt/FOXO3a signaling pathway. Finally, our results demonstrated that IBP-mediated breast cancer cell growth in vitro and in vivo was strongly correlated with suppression of mTORC2-dependent autophagy. These findings suggest that the anti-autophagic property of IBP has an important role in IBP-mediated tumorigenesis, and IBP may serve as an attractive target for treatment of breast cancer.

High-grade glioma is a malignant tumour; the pathogenesis is to be further investigated. Interleukin (IL)-17 is an inflammatory cytokine. Chronic inflammation is a pathological feature of cancer. This study aimed to characterize the glioma-derived IL-17 + regulatory T cells (Treg). In this study, single cells were isolated from surgically removed high-grade glioma tissue and examined by flow cytometry. The immune suppressor effect of IL-17 + Tregs on CD8 + T cells was assessed in vitro. The results showed that abundant IL-17 + Tregs were found in high-grade glioma tissue. The immune suppressor molecule, transforming growth factor (TGF)-beta, was detected in the IL-17 + Tregs. The proliferation of CD8 + T cells was suppressed by culturing with the IL-17 + Tregs, which was partially abrogated by neutralizing antibodies of either TGF-beta or IL-17 and completely abrogated by neutralizing antibodies against both TGF-beta and IL-17. In conclusion, IL-17 + Tregs exist in the high-grade glioma tissue; this subset of T cells can suppress CD8 + T cell activities via releasing TGF-beta and IL-17.

Suppressor of cytokine signalling (SOCS) proteins are crucial negative regulators in many signalling pathways and are implicated in the pathogenesis of infectious diseases. The purpose of this study was to uncover possible associations of common polymorphisms within SOCS genes with infectious outcomes after traumatic injury. A total of 1087 trauma patients (Chongqing cohort 806 and Yunnan cohort 281) were recruited and followed-up for the development of infectious outcomes, such as sepsis and multiple organ dysfunction syndrome (MODS). Twelve selected single nucleotide polymorphisms (SNPs) were screened by pyrosequencing to determine their genotypes and associations with infectious complications. Among the 12 selected SNPs, only the cytokine-inducible Src homology (SH2) domain protein (CISH) promoter rs414171 polymorphism was found consistently to be associated statistically with the incidence of sepsis and MOD score in the two cohorts, despite analysing the SNPs independently or in combination. Further, patients with a T allele had significantly lower CISH expression and lower production of tumour necrosis factor (TNF)-α, but higher production of interleukin (IL)-10. Luciferase assay confirmed that the A→T variant in the rs414171 polymorphism inhibited the transcriptional activities of the CISH gene significantly. The CISH rs414171 polymorphism is associated significantly with susceptibility to sepsis and MODS in traumatic patients, which might prove to be a novel biomarker for indicating risk of infectious outcomes in critically injured patients.

Objective Adverse environmental exposure inuteropredisposes to adult disease, including hypertension. Exposure to lipopolysaccharide (LPS) results in increased blood pressure in offspring, but the exact mechanisms are not clear. Our previous study shows dysfunction of renal D1receptor (D1R) isascribed to the pathogenesis of hypertension, which is associated with reactive oxidativestress (ROS). In this study, we test whether dysfunction of renal D1R is involved in fetal programmed hypertension, and whether oxidative stress contribute to this process. Methods Pregnant Sprague–Dawley (SD) rats were intraperitoneally injected with LPS (0.79 mg/kg) or saline (0.5 ml) at gestation day 8, 10 and 12. After birth, the blood pressure is measured, and treated with or without antioxidant tempol in tap water for 3 weeks at postnatal 12 week. Results As compared with control rats, the LPS-treated offspring rats showed higher blood pressure, decreased renal sodium excretion with increased plasma ROS activity. After treatment with tempol for 3 week, the increased blood pressure, decreased sodium excretion were reversed to normal levels in LPS rats. Our further study found LPS rats had lower renal D1R expression, higher D1R phosphorylation, and D1R-mediated natriuresis and diuresis were lost. As an important kinase of D1R phosphorylation, G coupled receptor protein kinase 4 (GRK4) expression was increased in LPS rats. Tempol treatment reversed the decreased D1R expression, increased D1R phosphorylation and GRK4 expression. Moreover, the impaired D1R-mediated natriuresis and diuresis were restored to the control levels in LPS rats after tempol treatment. Conclusion Pprenatal LPS exposure, via impairment of ROS on renal D1R function, leads to hypertension in offspring. Reversion of renal D1R function by alleviation of ROS might be a target for therapy of fetal programming hypertension.