Quercetin is a herbal flavonoid derived from various foods of plant origin and plays a role in anti-inflammation. Although a number of researches in the field have been done, the mechanism of anti-inflammatory effect ...Quercetin is a herbal flavonoid derived from various foods of plant origin and plays a role in anti-inflammation. Although a number of researches in the field have been done, the mechanism of anti-inflammatory effect of quercetin should be further darified. In the present study, we investigated the effects of quercetin on IL-6 production by LPS-stimulated neutrophils in human. Neutrophils were were pre-treated with quercetin at the final concentrations of ranging from 0-80 ~M for 30 rain, or not treated, and then incubated in the presence or absence of lipopolysaccharide （LPS） at a final concentration of 100 ng/ml for indicated time. The secretion level of IL-6 in the culture supernatants was assayed by ELISA, the intracellular level of IL-6 was detected by flow cytometry and the expression of IL-6 mRNA was analyzed by RT-PCR. The experiment results showed that neutrophils cultured with medium or quercetin alone did not express IL-6, but LPS （100 ng/ml） induced IL-6 expression of neutrophils. However, after pre-treatment of neutrophils with quercetin （40 ~Vl） for 30 rain, the inducible effects of LPS on the increase of IL-6 secretion, intracellular IL-6 level and IL-6 mRNA expression by neutrophils were abrogated. IL-6 is one of the important pro-inflammatory factors, especially in early phage of inflammation. Thus, our data suggested that quercetin might exert its anti-inflammatory effect through negatively modulating pro-inflammatory factors, such as IL-6. The inhibitory effects of quercetin on IL-6 production by neutrophils may provide a theoretical basis on future therapy of inflammation. Cellular ＆ Molecular Immunology. 2005;2（6）：455-460.展开更多
MicroRNAs(miRNAs)function as important regulators in the immune response and inflammation.Several approaches have been reported to computationally predict miRNAs and their potential targets.However,there are still man...MicroRNAs(miRNAs)function as important regulators in the immune response and inflammation.Several approaches have been reported to computationally predict miRNAs and their potential targets.However,there are still many miRNA–target interactions that are unpredictable by using the current computational algorithms.We established a miRNA in vivo precipitation method(miRIP)to identify unpredictable miRNAs with definite targets in these cells.Because Stat3 is a well-known transcription factor involved in innate immunity and inflammation,we utilized the miRIP method to identify miRNAs that bind Stat3 mRNA in macrophages.Among the captured miRNAs,miR-151-3p was confirmed to interact with Stat3 mRNA 3′-UTR and downregulate the Stat3 protein levels.LPS stimulation decreased miR-151-3p expression,thereby increasing IL-6 production.Therefore,we found that miR-151-3p inhibited LPS-induced IL-6 production by targeting Stat3.These data further confirmed miRIP as an efficient method to identify unpredictable miRNAs and explore miRNAs-mediated regulation in innate immunity and inflammation.展开更多
IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully...IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully elucidated.Here,we report that lysine-specific demethylase 2b(KDM2B),which demethylates H3K4me3 and H3K36me2,is required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α,IL-1,and IFN-β.Compared to wild-type mice,KDM2B-deficient mice were more resistant to endotoxin shock and colitis,with a less severe inflammatory pathogenesis phenotype and decreased IL-6 production in sera.KDM2B selectively bound the Il6 promoter but did not alter histone demethylation;instead,KDM2B interacted with Brahma-related gene 1(Brg1),the core ATPase subunit of SWI/SNF chromatin remodeling complexes,to facilitate chromatin accessibility of the Il6 promoter.Furthermore,KDM2B directly recruited RNA Polymerase II to further initiate and promote Il6 transcription.Thus,our finding identifies a novel nonclassical function of KDM2B in gene-specific transcription initiation and enhancement of Il6 independent of its demethylase activity and adds new insight into the specific epigenetic modification mechanism of inflammatory immune responses.展开更多
Many G protein-coupled receptors （GPCRs） are reported to be involved in the pathogenesis of multiple sclerosis （MS）, and -40% of all identified GPCRs rely on the Gaq/11 G protein family to stimulate inositol lipid...Many G protein-coupled receptors （GPCRs） are reported to be involved in the pathogenesis of multiple sclerosis （MS）, and -40% of all identified GPCRs rely on the Gaq/11 G protein family to stimulate inositol lipid signaling. However, the function of Ga subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gaq in the pathogenesis of experimental autoimmune encephalomyelitis （EAE）, a well-known mouse model of MS. We discovered that compared with wild-type mice, Gaq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gaq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gaq in CD4＋ T cells directly impaired Th17 differentiation. In addition, deficiency of Gaq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gaq-PLCβ-PKC and Gaq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gaq in regulating Th17 differentiation and MS oathogenesis.展开更多
Hybrid rice Xinhunyou No. 6 could be cultivated by mixing male and fe- male parents and performing seedling raising followed by transplanting, mechanical planting or mechanical direct seeding according to the producti...Hybrid rice Xinhunyou No. 6 could be cultivated by mixing male and fe- male parents and performing seedling raising followed by transplanting, mechanical planting or mechanical direct seeding according to the production methods of com- mercial rice. During flowering stage, leaf cutting, application of ＂920＂ and pollination were conducted; after pollination, bentazon with a certain concentration was sprayed to kill the male parent; and the hybrid rice was harvested mechanically. Before storage, color separation was performed to remove little remaining male parent, thereby achieving whole-process mechanization of hybrid rice seed production. This study introduced mechanized seed production of Xinhunyou No. 6 through mixed- seeding from the aspects including mechanical direct seeding, seeding raising fol- lowed by transplanting and mechanical planting.展开更多
文摘Quercetin is a herbal flavonoid derived from various foods of plant origin and plays a role in anti-inflammation. Although a number of researches in the field have been done, the mechanism of anti-inflammatory effect of quercetin should be further darified. In the present study, we investigated the effects of quercetin on IL-6 production by LPS-stimulated neutrophils in human. Neutrophils were were pre-treated with quercetin at the final concentrations of ranging from 0-80 ~M for 30 rain, or not treated, and then incubated in the presence or absence of lipopolysaccharide （LPS） at a final concentration of 100 ng/ml for indicated time. The secretion level of IL-6 in the culture supernatants was assayed by ELISA, the intracellular level of IL-6 was detected by flow cytometry and the expression of IL-6 mRNA was analyzed by RT-PCR. The experiment results showed that neutrophils cultured with medium or quercetin alone did not express IL-6, but LPS （100 ng/ml） induced IL-6 expression of neutrophils. However, after pre-treatment of neutrophils with quercetin （40 ~Vl） for 30 rain, the inducible effects of LPS on the increase of IL-6 secretion, intracellular IL-6 level and IL-6 mRNA expression by neutrophils were abrogated. IL-6 is one of the important pro-inflammatory factors, especially in early phage of inflammation. Thus, our data suggested that quercetin might exert its anti-inflammatory effect through negatively modulating pro-inflammatory factors, such as IL-6. The inhibitory effects of quercetin on IL-6 production by neutrophils may provide a theoretical basis on future therapy of inflammation. Cellular ＆ Molecular Immunology. 2005;2（6）：455-460.
基金We thank Dr Taoyong Chen and Dr Mingjin Yang for helpful discussion and Ms Mei Jin for technical assistanceThis work was supported by Grants from the National Key Basic Research Program of China(2013CB530502,2015CB964403)+1 种基金the National Natural Science Foundation of China(31470849,31390431 and 81471569)the Shanghai Committee of Science and Technology(2015QA1404700).
文摘MicroRNAs(miRNAs)function as important regulators in the immune response and inflammation.Several approaches have been reported to computationally predict miRNAs and their potential targets.However,there are still many miRNA–target interactions that are unpredictable by using the current computational algorithms.We established a miRNA in vivo precipitation method(miRIP)to identify unpredictable miRNAs with definite targets in these cells.Because Stat3 is a well-known transcription factor involved in innate immunity and inflammation,we utilized the miRIP method to identify miRNAs that bind Stat3 mRNA in macrophages.Among the captured miRNAs,miR-151-3p was confirmed to interact with Stat3 mRNA 3′-UTR and downregulate the Stat3 protein levels.LPS stimulation decreased miR-151-3p expression,thereby increasing IL-6 production.Therefore,we found that miR-151-3p inhibited LPS-induced IL-6 production by targeting Stat3.These data further confirmed miRIP as an efficient method to identify unpredictable miRNAs and explore miRNAs-mediated regulation in innate immunity and inflammation.
基金We thank X.Sun and M.Jin for technical assistance.This work was supported by the National Natural Science Foundation of China(31570871,81571541,81771695,31770970,and 81770094)Program of Shanghai Chief Scientist of Medical and Health Subject(2018BR16)Shuguang Program sponsored by the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(18SG33).
文摘IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully elucidated.Here,we report that lysine-specific demethylase 2b(KDM2B),which demethylates H3K4me3 and H3K36me2,is required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α,IL-1,and IFN-β.Compared to wild-type mice,KDM2B-deficient mice were more resistant to endotoxin shock and colitis,with a less severe inflammatory pathogenesis phenotype and decreased IL-6 production in sera.KDM2B selectively bound the Il6 promoter but did not alter histone demethylation;instead,KDM2B interacted with Brahma-related gene 1(Brg1),the core ATPase subunit of SWI/SNF chromatin remodeling complexes,to facilitate chromatin accessibility of the Il6 promoter.Furthermore,KDM2B directly recruited RNA Polymerase II to further initiate and promote Il6 transcription.Thus,our finding identifies a novel nonclassical function of KDM2B in gene-specific transcription initiation and enhancement of Il6 independent of its demethylase activity and adds new insight into the specific epigenetic modification mechanism of inflammatory immune responses.
基金This work was supported by grants from the Ministry of Science and Technology of China （2014CB541903, 2012CB910404）, the National Natural Science Foundation of China （31171348, 31371414）, the Shanghai Municipal Education Commission （14zz042）, the State Key Laboratory of Drug Research （SIMM1302KF-09） and the Fundamental Research Funds for the Central Universities.
文摘Many G protein-coupled receptors （GPCRs） are reported to be involved in the pathogenesis of multiple sclerosis （MS）, and -40% of all identified GPCRs rely on the Gaq/11 G protein family to stimulate inositol lipid signaling. However, the function of Ga subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gaq in the pathogenesis of experimental autoimmune encephalomyelitis （EAE）, a well-known mouse model of MS. We discovered that compared with wild-type mice, Gaq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gaq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gaq in CD4＋ T cells directly impaired Th17 differentiation. In addition, deficiency of Gaq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gaq-PLCβ-PKC and Gaq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gaq in regulating Th17 differentiation and MS oathogenesis.
基金Supported by Science and Technology Innovation Team of Anhui Academy of Agricultural Sciences(15C0108)Subject Construction Project of Anhui Academy of Agricultural Sciences(14A0102)Science and Technology Support Program of Ministry of Science and Technology(2012BAD07B01-3)~~
文摘Hybrid rice Xinhunyou No. 6 could be cultivated by mixing male and fe- male parents and performing seedling raising followed by transplanting, mechanical planting or mechanical direct seeding according to the production methods of com- mercial rice. During flowering stage, leaf cutting, application of ＂920＂ and pollination were conducted; after pollination, bentazon with a certain concentration was sprayed to kill the male parent; and the hybrid rice was harvested mechanically. Before storage, color separation was performed to remove little remaining male parent, thereby achieving whole-process mechanization of hybrid rice seed production. This study introduced mechanized seed production of Xinhunyou No. 6 through mixed- seeding from the aspects including mechanical direct seeding, seeding raising fol- lowed by transplanting and mechanical planting.
