The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim...The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression.Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines.Moreover,two novel positive regulatory elements,an enhancer-like element at 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)located in the Ig promoter,a crucial element for B-cell-derived Ig gene transcription,was also very important for non-B-cell-derived Ig gene transcription.More importantly,we confirmed that octamer-related protein-1(Oct-1),but not Oct-2,was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells.These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.展开更多
目的：探讨脓毒症单核细胞表达ILT4的生物学行为和效应，及对于预后的影响。方法：选取BALB/c、BALB/c ILT4–/–雄性小鼠，CLP复制脓毒症模型。用流式细胞仪定量检测CLP术后24h单核细胞ILT4、MHC-Ⅱ表达水平；用ELISA法检测各组0、6、1...目的：探讨脓毒症单核细胞表达ILT4的生物学行为和效应，及对于预后的影响。方法：选取BALB/c、BALB/c ILT4–/–雄性小鼠，CLP复制脓毒症模型。用流式细胞仪定量检测CLP术后24h单核细胞ILT4、MHC-Ⅱ表达水平；用ELISA法检测各组0、6、12、24h血清IL-6、TNF-α浓度；并观察168h内生存预后。 结果：CLP术后24小时脓毒症小鼠外周单核细胞高度表达ILT4分子 （193.50 ± 52.54 vs. 1292.00 ± 143.70, p 〈 0.05） ；较WT组ILT4–/–小鼠外周单核细胞表达MHC-Ⅱ比率明显增高（24.25± 6.76% vs. 49.38 ±5.66%, p 〈 0.05） 。CLP术后24h血清IL-6显著增高（54.25± 20.04 vs. 470.75±88.03, p 〈 0.05），ILT4敲除后很大程度的抑制这一趋势（470.75±88.03 vs. 241.25 ± 45.10, p 〈 0.05）；但对TNF-α表达无显著性干扰（53.13 ±5.49 vs. 50.88 ±6.38, p〉 0.05）。且ILT4–/–小鼠CLP术后生存率WT明显增加（p 〈 0.05）。结论：脓毒症时单核细胞高表达ILT4，与高IL-6水平及低MHC-Ⅱ表达率相关，导致死亡率增加。展开更多
The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determin...The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.展开更多
基金supported by Fundamental Research Grants 30572094 and 30772470 from the Natural Sciences Foundation,China.We thank Dr Dalong Ma and Dr Mingxu Xu(Peking University Center for Human Disease Genomics)for their comments and suggestions.This manuscript was proofread by an English-speaking professional with a science background at Elixigen Corporation.
文摘The restriction of immunoglobulin(Ig)expression to B lymphocytes is well established.However,several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells.Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression.Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines.Moreover,two novel positive regulatory elements,an enhancer-like element at 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)located in the Ig promoter,a crucial element for B-cell-derived Ig gene transcription,was also very important for non-B-cell-derived Ig gene transcription.More importantly,we confirmed that octamer-related protein-1(Oct-1),but not Oct-2,was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells.These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.
文摘目的：探讨脓毒症单核细胞表达ILT4的生物学行为和效应，及对于预后的影响。方法：选取BALB/c、BALB/c ILT4–/–雄性小鼠，CLP复制脓毒症模型。用流式细胞仪定量检测CLP术后24h单核细胞ILT4、MHC-Ⅱ表达水平；用ELISA法检测各组0、6、12、24h血清IL-6、TNF-α浓度；并观察168h内生存预后。 结果：CLP术后24小时脓毒症小鼠外周单核细胞高度表达ILT4分子 （193.50 ± 52.54 vs. 1292.00 ± 143.70, p 〈 0.05） ；较WT组ILT4–/–小鼠外周单核细胞表达MHC-Ⅱ比率明显增高（24.25± 6.76% vs. 49.38 ±5.66%, p 〈 0.05） 。CLP术后24h血清IL-6显著增高（54.25± 20.04 vs. 470.75±88.03, p 〈 0.05），ILT4敲除后很大程度的抑制这一趋势（470.75±88.03 vs. 241.25 ± 45.10, p 〈 0.05）；但对TNF-α表达无显著性干扰（53.13 ±5.49 vs. 50.88 ±6.38, p〉 0.05）。且ILT4–/–小鼠CLP术后生存率WT明显增加（p 〈 0.05）。结论：脓毒症时单核细胞高表达ILT4，与高IL-6水平及低MHC-Ⅱ表达率相关，导致死亡率增加。
基金We thank Dr.Jiangbo Song for phylogenetic analysis.This research was funded by National Natural Science Foundation of China(31872428 and 31872427)Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0096 and estc 2020jscx-msxmX0045)China Agriculture Research System(CARS-18).
文摘The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.
