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BackgroundRecent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of the alteration remains unclear.MethodsWe cultured monocyte-derived DCs (moDCs) in vitro and examined the cytokines and chemokines in the supernatants of moDCs in negative controls (NC) and SLE patients in active phase. We then profiled microRNAs (miRNAs) of LPS-stimulated moDCs in SLE patients and used real-time PCR to verify the differentially expressed miRNAs. A lentiviral construct was used to overexpress the level of miR-142-3p in moDCs of NC. We examined the cytokines and chemokines in the supernatants of moDCs overexpressing miR-142-3p and used Transwell test, flow cytometric analysis and cell proliferation to observe the impact on CD4+ T cells in moDC-CD4+T cell co-culture.ResultsmoDCs in patients with SLE secreted increased level of IL-6, CCL2 and CCL5, with attraction of more CD4+ T cells compared with NC. We found 18 differentially expressed microRNAs in moDCs of SLE patients by microarray, and target gene prediction showed some target genes of differentially expressed miRNAs were involved in cytokine regulation. miR-142-3p was verified among the highly expressed miRNAs in the SLE group and overexpressing miR-142-3p in moDCs of the NC group caused an increase of SLE-related cytokines, such as CCL2, CCL5, CXCL8, IL-6 and TNF-α. Moreover, moDCs overexpressed with miR-142-3p resulted in attraction of an increased number of CD4+ T cells and in suppression of the proportion of Tregs in DC-CD4+T cell co-culture whereas the proliferation of CD4+T cells was not altered.ConclusionsThe results demonstrated a role for miR-142-3p in regulating the pro-inflammatory function of moDCs in the pathogenesis of SLE. These findings suggested that miR-142-3p could serve as a novel therapeutic target for the treatment of SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1158-z) contains supplementary material, which is available to authorized users.

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BackgroundMonocyte-derived dendritic cells (moDCs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Aberrant expression of long noncoding RNAs (lncRNAs) could affect the function of moDCs. The aim of this study was to explore the lncRNA expression profile in moDCs of SLE patients to provide new insights into SLE.MethodsLncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in moDCs of SLE patients compared with normal controls. Bioinformatics analysis was also performed. Quantitative polymerase chain reaction (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and SLE disease activity index (SLEDAI) scores.ResultsAccording to the gene expression profiles, 163 lncRNAs were differentially expressed between SLE and normal controls, including 118 that were upregulated and 45 that were downregulated. A total of 137 mRNAs were differentially expressed in moDCs of patients with SLE, including 83 that were upregulated and 54 that were downregulated. Furthermore, qPCR data showed that lncRNA ENST00000604411.1 (18.23-fold, P < 0.001) and ENST00000501122.2 (1.96-fold, P < 0.001) were upregulated and the other two lncRNAs, lnc-HSFY2–3:3 (0.42-fold, P < 0.001) and lnc-SERPINB9–1:2 (0.50-fold, P = 0.040), were downregulated in moDCs of SLE patients. The expression levels of ENST00000604411.1 (r = 0.593, P = 0.020) and ENST00000501122.2 (r = 0.539, P = 0.038) were positively correlated with the SLEDAI score, respectively.ConclusionsThe results indicate that the abnormal expression of lncRNAs in moDCs may be involved in the pathological processes of SLE. The expression level of ENST00000604411.1 and ENST00000501122.2 may have potential value for the assessment of disease activity in SLE.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1640-x) contains supplementary material, which is available to authorized users.

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Improvements in skin cancer treatment are likely to derive from novel agents targeting the molecular pathways that promote tumor cell growth and survival. Icariside II (IS) is a metabolite of icariin, which is derived from Herba Epimedii. The aim of the present study was to evaluate the antitumor effects of IS and to determine the mechanism of apoptosis in A431 human epidermoid carcinoma cells. A431 cells were treated with IS (0‑100 µM) for 24 or 48 h and cell viability was detected using the WST‑8 assay. Apoptosis was measured by the Annexin‑V/propidium iodide (PI) flow cytometric assay. Western blot analysis was used to measure the expression of cleaved caspase‑9, cleaved poly ADP ribose polymerase (PARP), phosphorylated signal transducer and activator of transcription 3 (P‑STAT3), phosphorylated extracellular signal-regulated kinase (P‑ERK), and P‑AKT. A431 cells were also pretreated with IS (0‑100 µM) 2 h prior to treatment with epidermal growth factor (EGF; 100 ng/ml) for 10 min. Phosphorylated EGF receptor (P‑EGFR), P‑STAT3, P‑ERK and P‑AKT were detected by western blot analysis. The results demonstrated that IS inhibited the cell viability of the A431 cells in a dose‑dependent manner. Pretreatment with LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor], EGF (an EGFR agonist) and AG1478 (an EGFR inhibitor) partially reversed IS‑induced decreases in cell viability. Treatment with 50 µm IS resulted in an increased number of apoptotic cells mirrored by increases in cleaved caspase‑9 and cleaved PARP. In addition, treatment with 50 µM IS significantly inhibited the activation of the Janus kinase (JAK)‑STAT3 and mitogen‑activated protein kinase (MAPK)‑ERK pathways, but promoted the activation of the PI3K‑AKT pathway. Furthermore, IS effectively inhibited the EGF-induced activation of the EGFR pathways. In conclusion, IS inhibited the cell viability of the A431 cells through the regulation of apoptosis. These effects were mediated, at least in part, by inhibiting the activation of the EGFR pathways.

Ultraviolet (UV) light is one of the most harmful environmental factors that contribute to skin damage. Exposure to UV induces extensive generation of reactive oxygen species (ROS), and results in photoaging and skin cancer development. One approach to protecting human skin against UV radiation is the use of antioxidants. In recent years, naturally occurring herbal compounds have gained considerable attention as protective agents for UV exposure. Paeoniflorin (PF) is a novel natural antioxidant, which is isolated from peony root (Radix Paeoniae Alba). The present study evaluated the protective effects of PF on UV‑induced skin damage in vitro, and demonstrated that the effects were mediated via the ROS‑p38‑p53 pathway. The results of the present study demonstrated that treatment with PF (25, 50, and 100 µM) significantly increased the percentage of viable keratinocytes after UV‑B exposure. In addition, cell death analysis indicated that PF treatment markedly reduced UV‑B‑radiation‑induced apoptosis in keratinocytes, which was accompanied by increased procaspase 3 expression and decreased cleaved caspase 3 expression. Treatment with PF markedly reduced the production of ROS, and inhibited the activation of p38 and p53 in human keratinocytes, thus suggesting that the ROS‑p38‑p53 pathway has a role in UV‑B‑induced skin damage. In conclusion, the present study reported that PF was able to attenuate UV‑B‑induced cell damage in human keratinocytes. Notably, these effects were shown to be mediated, at least in part, via inhibition of the ROS-p38-p53 pathway.

The recent report highlighted a significant association between signal transducer and activator of transcription 3 (STAT3) and Snail and LIV-1 (SLC39A6 or ZIP6), the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. LIV-1 is a downstream target of STAT3, both in zebrafish and mammalian cells and provides control over epithelial-mesenchymal transition (EMT). Crucially, these observations link LIV-1, previously demonstrated to be associated with lymph node metastasis in breast cancer, to genes with a proven role in development. A putative role of LIV-1 as a regulator of E-cadherin that modulates the cell-cell adhesion is thus inferred. In present study, the correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7 and the effect of LIV-1 expression on the cell growth were assessed to explore the possible mechanisms associated with this observation in breast cancer. It was shown that the silencing of LIV-1 would induce the down-expression of E-cadherin. There was opposite results if the cells were overexpressed with LIV-1. In addition, the results showed that promotion effect after silencing of LIV-1 and inhibition effect after overexpression of LIV-1 in transfected cells. To our knowledge, this is the first evidence that the expression of E-cadherin could be regulated by the zinc transporter LIV-1. The results suggest that there is an association of LIV-1 expression with less aggressive tumors due to high E-cadherin expression because of high LIV-1 expression. LIV-1 may be a regulator of E-cadherin.