AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patient...AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.展开更多
AIM: To investigate the role of mi R-125 b in regulating monocyte immune responses induced by hepatitis C virus(HCV) core protein.METHODS: Monocytic THP-1 cells were treated with various concentrations of recombinant ...AIM: To investigate the role of mi R-125 b in regulating monocyte immune responses induced by hepatitis C virus(HCV) core protein.METHODS: Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and mi R-125 b expression in these cells were analyzed. The requirement of Tolllike receptor 2(TLR2) or My D88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 si RNA or My D88 si RNA. The effect of mi R-125 b overexpression on TLR2/My D88 signaling was examined by transfecting THP-1 cells with mi R-125 b mimic RNA oligos.RESULTS: In response to HCV core protein stimulation, cytokine production was up-regulated and mi R-125 b expression was down-regulated in THP-1 cells. The modulatory effect of HCV core protein on cellular events was dose-dependent and required functional TLR2 or My D88 gene. Forced mi R-125 b expression abolished the HCV core protein-induced enhancement of tumor necrosis factor-α, interleukin(IL)-6, and IL-10 expression by 66%, 54%, and 66%, respectively(P < 0.001), by inhibiting My D88-mediated signaling, including phosphorylation of NF-k Bp65, ERK, and P38.CONCLUSION: The inverse correlation between mi R-125 b and cytokine expression after HCV core challenge suggests that mi R-125 b may negatively regulate HCVinduced immune responses by targeting TLR2/My D88 signaling in monocytes.展开更多
The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator,...The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.展开更多
文摘AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.
基金Supported by National Natural Science Foundation of China, No. 81202321 and No. 81461130019Transregio-SFB (TRR) of the Deutsche Forschungsgemeinschaft (DFG), No. TRR60
文摘AIM: To investigate the role of mi R-125 b in regulating monocyte immune responses induced by hepatitis C virus(HCV) core protein.METHODS: Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and mi R-125 b expression in these cells were analyzed. The requirement of Tolllike receptor 2(TLR2) or My D88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 si RNA or My D88 si RNA. The effect of mi R-125 b overexpression on TLR2/My D88 signaling was examined by transfecting THP-1 cells with mi R-125 b mimic RNA oligos.RESULTS: In response to HCV core protein stimulation, cytokine production was up-regulated and mi R-125 b expression was down-regulated in THP-1 cells. The modulatory effect of HCV core protein on cellular events was dose-dependent and required functional TLR2 or My D88 gene. Forced mi R-125 b expression abolished the HCV core protein-induced enhancement of tumor necrosis factor-α, interleukin(IL)-6, and IL-10 expression by 66%, 54%, and 66%, respectively(P < 0.001), by inhibiting My D88-mediated signaling, including phosphorylation of NF-k Bp65, ERK, and P38.CONCLUSION: The inverse correlation between mi R-125 b and cytokine expression after HCV core challenge suggests that mi R-125 b may negatively regulate HCVinduced immune responses by targeting TLR2/My D88 signaling in monocytes.
基金National Natural Science Foundation of China(21322705,41121004,21190051,and 21177091)
文摘The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.
