Journal of signal transduction最新文献

Thyroid Hormones as Renal Cell Cancer Regulators 甲状腺激素作为肾细胞癌的调节因子

Journal of signal transduction Pub Date : 2016-03-13 DOI: 10.1155/2016/1362407

Łukasz Szymański, Damian Matak, E. Bartnik, C. Szczylik, A. Czarnecka

引用次数: 11

Analysis of AKAP7γ Dimerization. AKAP7γ二聚化分析。

Journal of signal transduction Pub Date : 2015-01-01 Epub Date: 2015-08-31 DOI: 10.1155/2015/371626

Arpita Singh, Marc Rigatti, Andrew V Le, Cathrine R Carlson, Ion I Moraru, Kimberly L Dodge-Kafka

{"title":"Analysis of AKAP7γ Dimerization.","authors":"Arpita Singh, Marc Rigatti, Andrew V Le, Cathrine R Carlson, Ion I Moraru, Kimberly L Dodge-Kafka","doi":"10.1155/2015/371626","DOIUrl":"https://doi.org/10.1155/2015/371626","url":null,"abstract":"A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that contribute to spatiotemporal regulation of PKA-mediated phosphorylation events. In particular, AKAP7 is a family of alternatively spliced proteins that participates in cardiac calcium dynamics. Here, we demonstrate via pull-down from transfected cells and by direct protein-protein association that AKAP7γ self-associates. Self-association appears to be an isoform specific phenomenon, as AKAP7α did not associate with itself or with AKAP7γ. However, AKAP7γ did associate with AKAP7δ, suggesting the long isoforms of the AKAP can form heterodimers. Surface plasmon resonance found that the AKAP7γ self-association occurs via two high affinity binding sites with K D values in the low nanomolar range. Mapping of the binding sites by peptide array reveals that AKAP7γ interacts with itself through multiple regions. Photon counting histogram analysis (PCH) of AKAP7γ-EGFP expressed in HEK-293 cells confirmed that AKAP7γ-EGFP self-associates in a cellular context. Lastly, computational modeling of PKA dynamics within AKAP7γ complexes suggests that oligomerization may augment phosphorylation of scaffolded PKA substrates. In conclusion, our study reveals that AKAP7γ forms both homo- and heterodimers with the long isoforms of the AKAP and that this phenomenon could be an important step in mediating effective substrate phosphorylation in cellular microdomains. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2015 ","pages":"371626"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/371626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34113221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling. 磷酸酶和紧张素同系物:发育信号的新调控。

Journal of signal transduction Pub Date : 2015-01-01 Epub Date: 2015-08-03 DOI: 10.1155/2015/282567

Travis J Jerde

{"title":"Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling.","authors":"Travis J Jerde","doi":"10.1155/2015/282567","DOIUrl":"https://doi.org/10.1155/2015/282567","url":null,"abstract":"Phosphatase and tensin homologue (PTEN) is a critical cell endogenous inhibitor of phosphoinositide signaling in mammalian cells. PTEN dephosphorylates phosphoinositide trisphosphate (PIP3), and by so doing PTEN has the function of negative regulation of Akt, thereby inhibiting this key intracellular signal transduction pathway. In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells. Numerous reports exist regarding mutations in PTEN leading to unregulated Akt and human disease, most notably cancer. However, less is commonly known about nonmutational regulation of PTEN. This review focuses on an emerging literature on the regulation of PTEN at the transcriptional, posttranscriptional, translational, and posttranslational levels. Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling. The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival. Perturbations of PTEN regulation consequently lead to human diseases such as cancer, chronic inflammatory syndromes, developmental abnormalities, diabetes, and neurodegeneration. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2015 ","pages":"282567"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/282567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34147815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system. 参与肾氧化损伤的信号通路:血管活性肽和肾多巴胺能系统的作用。

Journal of signal transduction Pub Date : 2014-01-01 Epub Date: 2014-11-11 DOI: 10.1155/2014/731350

N L Rukavina Mikusic, M C Kravetz, N M Kouyoumdzian, S L Della Penna, M I Rosón, B E Fernández, M R Choi

{"title":"Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.","authors":"N L Rukavina Mikusic, M C Kravetz, N M Kouyoumdzian, S L Della Penna, M I Rosón, B E Fernández, M R Choi","doi":"10.1155/2014/731350","DOIUrl":"https://doi.org/10.1155/2014/731350","url":null,"abstract":"The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2014 ","pages":"731350"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/731350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32848781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

A Network Map of FGF-1/FGFR Signaling System. FGF-1/FGFR信号系统的网络图谱。

Journal of signal transduction Pub Date : 2014-01-01 Epub Date: 2014-04-16 DOI: 10.1155/2014/962962

Rajesh Raju, Shyam Mohan Palapetta, Varot K Sandhya, Apeksha Sahu, Abbas Alipoor, Lavanya Balakrishnan, Jayshree Advani, Bijesh George, K Ramachandra Kini, N P Geetha, H S Prakash, T S Keshava Prasad, Yu-Jung Chang, Linyi Chen, Akhilesh Pandey, Harsha Gowda

{"title":"A Network Map of FGF-1/FGFR Signaling System.","authors":"Rajesh Raju, Shyam Mohan Palapetta, Varot K Sandhya, Apeksha Sahu, Abbas Alipoor, Lavanya Balakrishnan, Jayshree Advani, Bijesh George, K Ramachandra Kini, N P Geetha, H S Prakash, T S Keshava Prasad, Yu-Jung Chang, Linyi Chen, Akhilesh Pandey, Harsha Gowda","doi":"10.1155/2014/962962","DOIUrl":"https://doi.org/10.1155/2014/962962","url":null,"abstract":"Fibroblast growth factor-1 (FGF-1) is a well characterized growth factor among the 22 members of the FGF superfamily in humans. It binds to all the four known FGF receptors and regulates a plethora of functions including cell growth, proliferation, migration, differentiation, and survival in different cell types. FGF-1 is involved in the regulation of diverse physiological processes such as development, angiogenesis, wound healing, adipogenesis, and neurogenesis. Deregulation of FGF-1 signaling is not only implicated in tumorigenesis but also is associated with tumor invasion and metastasis. Given the biomedical significance of FGFs and the fact that individual FGFs have different roles in diverse physiological processes, the analysis of signaling pathways induced by the binding of specific FGFs to their cognate receptors demands more focused efforts. Currently, there are no resources in the public domain that facilitate the analysis of signaling pathways induced by individual FGFs in the FGF/FGFR signaling system. Towards this, we have developed a resource of signaling reactions triggered by FGF-1/FGFR system in various cell types/tissues. The pathway data and the reaction map are made available for download in different community standard data exchange formats through NetPath and NetSlim signaling pathway resources. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2014 ","pages":"962962"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/962962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32341518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 93

TGF- β Signaling Cooperates with AT Motif-Binding Factor-1 for Repression of the α -Fetoprotein Promoter. TGF- β信号与AT基序结合因子-1协同抑制α -胎蛋白启动子

Journal of signal transduction Pub Date : 2014-01-01 Epub Date: 2014-07-03 DOI: 10.1155/2014/970346

Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaoki, Naoko Nakano, Susumu Itoh

{"title":"TGF- β Signaling Cooperates with AT Motif-Binding Factor-1 for Repression of the α -Fetoprotein Promoter.","authors":"Nobuo Sakata, Satoshi Kaneko, Souichi Ikeno, Yutaka Miura, Hidekazu Nakabayashi, Xue-Yuan Dong, Jin-Tang Dong, Taiki Tamaoki, Naoko Nakano, Susumu Itoh","doi":"10.1155/2014/970346","DOIUrl":"https://doi.org/10.1155/2014/970346","url":null,"abstract":"α-Fetoprotein (AFP) is known to be highly produced in fetal liver despite its barely detectable level in normal adult liver. On the other hand, hepatocellular carcinoma often shows high expression of AFP. Thus, AFP seems to be an oncogenic marker. In our present study, we investigated how TGF-β signaling cooperates with AT motif-binding factor-1 (ATBF1) to inhibit AFP transcription. Indeed, the expression of AFP mRNA in HuH-7 cells was negatively regulated by TGF-β signaling. To further understand how TGF-β suppresses the transcription of the AFP gene, we analyzed the activity of the AFP promoter in the presence of TGF-β. We found that the TGF-β signaling and ATBF1 suppressed AFP transcription through two ATBF1 binding elements (AT-motifs). Using a heterologous reporter system, both AT-motifs were required for transcriptional repression upon TGF-β stimulation. Furthermore, Smads were found to interact with ATBF1 at both its N-terminal and C-terminal regions. Since the N-terminal (ATBF1N) and C-terminal regions of ATBF1 (ATBF1C) lack the ability of DNA binding, both truncated mutants rescued the cooperative inhibitory action by the TGF-β signaling and ATBF1 in a dose-dependent manner. Taken together, these findings indicate that TGF-β signaling can act in concert with ATBF1 to suppress the activity of the AFP promoter through direct interaction of ATBF1 with Smads. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2014 ","pages":"970346"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/970346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32570515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Signaling Network Map of Endothelial TEK Tyrosine Kinase. 内皮TEK酪氨酸激酶信号网络图谱。

Journal of signal transduction Pub Date : 2014-01-01 Epub Date: 2014-10-13 DOI: 10.1155/2014/173026

Aafaque Ahmad Khan, Varot K Sandhya, Priyata Singh, Deepak Parthasarathy, Awinav Kumar, Jayshree Advani, Rudrappa Gattu, Dhanya V Ranjit, Rama Vaidyanathan, Premendu Prakash Mathur, T S Keshava Prasad, F Mac Gabhann, Akhilesh Pandey, Rajesh Raju, Harsha Gowda

{"title":"Signaling Network Map of Endothelial TEK Tyrosine Kinase.","authors":"Aafaque Ahmad Khan, Varot K Sandhya, Priyata Singh, Deepak Parthasarathy, Awinav Kumar, Jayshree Advani, Rudrappa Gattu, Dhanya V Ranjit, Rama Vaidyanathan, Premendu Prakash Mathur, T S Keshava Prasad, F Mac Gabhann, Akhilesh Pandey, Rajesh Raju, Harsha Gowda","doi":"10.1155/2014/173026","DOIUrl":"https://doi.org/10.1155/2014/173026","url":null,"abstract":"TEK tyrosine kinase is primarily expressed on endothelial cells and is most commonly referred to as TIE2. TIE2 is a receptor tyrosine kinase modulated by its ligands, angiopoietins, to regulate the development and remodeling of vascular system. It is also one of the critical pathways associated with tumor angiogenesis and familial venous malformations. Apart from the vascular system, TIE2 signaling is also associated with postnatal hematopoiesis. Despite the involvement of TIE2-angiopoietin system in several diseases, the downstream molecular events of TIE2-angiopoietin signaling are not reported in any pathway repository. Therefore, carrying out a detailed review of published literature, we have documented molecular signaling events mediated by TIE2 in response to angiopoietins and developed a network map of TIE2 signaling. The pathway information is freely available to the scientific community through NetPath, a manually curated resource of signaling pathways. We hope that this pathway resource will provide an in-depth view of TIE2-angiopoietin signaling and will lead to identification of potential therapeutic targets for TIE2-angiopoietin associated disorders. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2014 ","pages":"173026"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/173026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32793180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines) Ameliorating Mood Disorders. 星形胶质细胞的信号转导在慢性或急性治疗药物(SSRIs，抗双相药物，gaba -能药物和苯二氮卓类药物)改善情绪障碍。

Journal of signal transduction Pub Date : 2014-01-01 Epub Date: 2014-02-24 DOI: 10.1155/2014/593934

Leif Hertz, Dan Song, Baoman Li, Ting Du, Junnan Xu, Li Gu, Ye Chen, Liang Peng

{"title":"Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines) Ameliorating Mood Disorders.","authors":"Leif Hertz, Dan Song, Baoman Li, Ting Du, Junnan Xu, Li Gu, Ye Chen, Liang Peng","doi":"10.1155/2014/593934","DOIUrl":"https://doi.org/10.1155/2014/593934","url":null,"abstract":"Chronic treatment with fluoxetine or other so-called serotonin-specific reuptake inhibitor antidepressants (SSRIs) or with a lithium salt \"lithium\", carbamazepine, or valproic acid, the three classical antibipolar drugs, exerts a multitude of effects on astrocytes, which in turn modulate astrocyte-neuronal interactions and brain function. In the case of the SSRIs, they are to a large extent due to 5-HT2B-mediated upregulation and editing of genes. These alterations induce alteration in effects of cPLA2, GluK2, and the 5-HT2B receptor, probably including increases in both glucose metabolism and glycogen turnover, which in combination have therapeutic effect on major depression. The ability of increased levels of extracellular K(+) to increase [Ca(2+)] i is increased as a sign of increased K(+)-induced excitability in astrocytes. Acute anxiolytic drug treatment with benzodiazepines or GABAA receptor stimulation has similar glycogenolysis-enhancing effects. The antibipolar drugs induce intracellular alkalinization in astrocytes with lithium acting on one acid extruder and carbamazepine and valproic acid on a different acid extruder. They inhibit K(+)-induced and transmitter-induced increase of astrocytic [Ca(2+)] i and thereby probably excitability. In several cases, they exert different changes in gene expression than SSRIs, determined both in cultured astrocytes and in freshly isolated astrocytes from drug-treated animals. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2014 ","pages":"593934"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/593934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32241588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

AP-1 Gene Expression Levels May Be Correlated with Changes in Gene Expression of Some Stemness Factors in Colon Carcinomas. AP-1基因表达水平可能与结肠癌中某些干细胞因子的基因表达变化有关。

Journal of signal transduction Pub Date : 2013-01-01 Epub Date: 2013-12-11 DOI: 10.1155/2013/497383

Panagiotis Apostolou, Maria Toloudi, Eleni Ioannou, Marina Chatziioannou, Eleni Kourtidou, Ioanna Vlachou, Ioannis Papasotiriou

{"title":"AP-1 Gene Expression Levels May Be Correlated with Changes in Gene Expression of Some Stemness Factors in Colon Carcinomas.","authors":"Panagiotis Apostolou, Maria Toloudi, Eleni Ioannou, Marina Chatziioannou, Eleni Kourtidou, Ioanna Vlachou, Ioannis Papasotiriou","doi":"10.1155/2013/497383","DOIUrl":"https://doi.org/10.1155/2013/497383","url":null,"abstract":"The AP-1 transcription factor is a heterodimer protein that regulates gene expression in response to a variety of extrinsic stimuli through signal transduction. It is involved in processes including differentiation, proliferation, and apoptosis. Among the genes it regulates are transcription factors that contribute to the stemness phenotype. Cancer stem cells have the ability to self-renew and initiate differentiation into heterogenic cancer cells, which may cause metastasis and relapses. In the present study, we evaluated the effect of AP-1 complexes, as well as the C-FOS and C-JUN genes, in relation to NANOG, OCT3/4, and SOX2 transcription factors. All assays were undertaken with colon cancer stem cells. Knockdown experiments with siRNA were performed for each individual gene as well as their combination. Changes in gene expression were calculated with quantitative polymerase chain reaction experiments, while the effect on cell cycle distribution and apoptosis was studied by flow cytometry. The results differed depending on the percentage of repression, as well as the gene that was suppressed. In all cases, the number of apoptotic cells was increased. These findings indicate that AP-1 may have a crucial role in the maintenance of cancer stem cells. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2013 ","pages":"497383"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/497383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32005488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

An fc gamma receptor-mediated upregulation of the production of interleukin 10 by intravenous immunoglobulin in bone-marrow-derived mouse dendritic cells stimulated with lipopolysaccharide in vitro. 体外脂多糖刺激小鼠骨髓源树突状细胞，经静脉注射免疫球蛋白介导的fc γ受体介导的白细胞介素10分泌上调。

Journal of signal transduction Pub Date : 2013-01-01 Epub Date: 2013-06-18 DOI: 10.1155/2013/239320

Akihiro Fujii, Yuko Kase, Chiaki Suzuki, Akihito Kamizono, Teruaki Imada

{"title":"An fc gamma receptor-mediated upregulation of the production of interleukin 10 by intravenous immunoglobulin in bone-marrow-derived mouse dendritic cells stimulated with lipopolysaccharide in vitro.","authors":"Akihiro Fujii, Yuko Kase, Chiaki Suzuki, Akihito Kamizono, Teruaki Imada","doi":"10.1155/2013/239320","DOIUrl":"https://doi.org/10.1155/2013/239320","url":null,"abstract":"Intravenous immunoglobulin (IVIG), a highly purified immunoglobulin fraction prepared from pooled plasma of several thousand donors, increased anti-inflammatory cytokine IL-10 production, while decreased proinflammatory cytokine IL-12p70 production in bone-marrow-derived mouse dendritic cells (BMDCs) stimulated with lipopolysaccharide (LPS). The changes of cytokine production were confirmed with the transcription levels of these cytokines. To study the mechanisms of this bidirectional effect, we investigated changes of intracellular molecules in the LPS-induced signaling pathway and observed that IVIG upregulated ERK1/2 phosphorylation while downregulated p38 MAPK phosphorylation. Using chemical inhibitors specific to protein kinases involved in activation of Fc gamma receptors (FcγRs), which mediate IgG signals, we found that hyperphosphorylation of ERK1/2 and Syk phosphorylation occurred after stimulation of BMDC with LPS and IVIG, and the increasing effect on IL-10 production was abolished by these inhibitors. Furthermore, an antibody specific to FcγRI, one of FcγRs involved in immune activation, inhibited IVIG-induced increases in IL-10 production, but not IL-12p70 decreases, whereas the anti-IL-10 antibody restored the decrease in IL-12p70 induced by IVIG. These findings suggest that IVIG induced the upregulation of IL-10 production through FcγRI activation, and IL-10 was indispensable to the suppressing effect of IVIG on the production of IL-12p70 in LPS-stimulated BMDC. ","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2013 ","pages":"239320"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/239320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31580682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11