Pub Date : 2018-12-01DOI: 10.1080/15419061.2018.1444034
Philip R Brauer, Jee Hun Kim, Humberto J Ochoa, Elizabeth R Stratton, Kathryn M Black, William Rosencrans, Eliza Stacey, Engda G Hagos
Kru¨ppel like factor 4 (KLF4) is a transcription factor that regulates genes related to differentiation and proliferation. KLF4 also plays a role in metastasis via epithelial to mesenchymal transition. Here, we investigate the function of Klf4 in migration and invasion using mouse embryonic fibroblasts and the RKO human colon cancer cell line. Compared to wild-type, cells lacking Klf4 exhibited increased migration-associated phenotypes. In addition, overexpression of Klf4 in Klf4-/- MEFs attenuated the presence of stress fibers to wild-type levels. An invasion assay suggested that lack of Klf4 resulted in increased invasive capacity. Finally, analysis of RhoA showed elevated RhoA activity in both RKO and MEF cells. Taken together, our results strongly support the novel role of KLF4 in a post-translational regulatory mechanism where KLF4 indirectly modulates the actin cytoskeleton morphology via activity of RhoA in order to inhibit cellular migration and invasion.
{"title":"Krüppel-like factor 4 mediates cellular migration and invasion by altering RhoA activity.","authors":"Philip R Brauer, Jee Hun Kim, Humberto J Ochoa, Elizabeth R Stratton, Kathryn M Black, William Rosencrans, Eliza Stacey, Engda G Hagos","doi":"10.1080/15419061.2018.1444034","DOIUrl":"https://doi.org/10.1080/15419061.2018.1444034","url":null,"abstract":"<p><p>Kru¨ppel like factor 4 (KLF4) is a transcription factor that regulates genes related to differentiation and proliferation. KLF4 also plays a role in metastasis via epithelial to mesenchymal transition. Here, we investigate the function of Klf4 in migration and invasion using mouse embryonic fibroblasts and the RKO human colon cancer cell line. Compared to wild-type, cells lacking Klf4 exhibited increased migration-associated phenotypes. In addition, overexpression of Klf4 in Klf4<sup>-/-</sup> MEFs attenuated the presence of stress fibers to wild-type levels. An invasion assay suggested that lack of Klf4 resulted in increased invasive capacity. Finally, analysis of RhoA showed elevated RhoA activity in both RKO and MEF cells. Taken together, our results strongly support the novel role of KLF4 in a post-translational regulatory mechanism where KLF4 indirectly modulates the actin cytoskeleton morphology via activity of RhoA in order to inhibit cellular migration and invasion.</p>","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"24 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15419061.2018.1444034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35876827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-01DOI: 10.1080/15419061.2018.1464000
Jing Kong, Han Zhao, Qianhui Shang, Zhifei Ma, Ni Kang, Junling Tan, Hyat Ahmed Ibrahim Alraimi, Tingjiao Liu
Salivary gland adenoid cystic carcinoma (SACC) is one of the most common malignancies in the oral and maxillofacial region. Carcinoma-associated fibroblast (CAF) is an important component in the tumor microenvironment and participates in SACC progression. In this study, we established a CAF cell line derived from a human SACC and named it CAF-SA. It was identified that CAF-SA expressed typical CAF biomarkers. Then, we studied the cellular communications between CAF-SA, tumor cells and endothelial cells. It was found that CAF-SA promoted the migration, invasion, and proliferation of SACC tumor cells in vitro. In addition, tube formation by endothelial cells was enhanced by CAF-SA. In vivo experiment showed that SACC cells formed larger xenografts in nude mice when they were transplanted with CAF-SA. Overall, we demonstrated that CAF-SA exhibited the most important defining feature of CAF by promoting cancer progression.
{"title":"Establishment and characterization of a carcinoma-associated fibroblast cell line derived from a human salivary gland adenoid cystic carcinoma.","authors":"Jing Kong, Han Zhao, Qianhui Shang, Zhifei Ma, Ni Kang, Junling Tan, Hyat Ahmed Ibrahim Alraimi, Tingjiao Liu","doi":"10.1080/15419061.2018.1464000","DOIUrl":"https://doi.org/10.1080/15419061.2018.1464000","url":null,"abstract":"<p><p>Salivary gland adenoid cystic carcinoma (SACC) is one of the most common malignancies in the oral and maxillofacial region. Carcinoma-associated fibroblast (CAF) is an important component in the tumor microenvironment and participates in SACC progression. In this study, we established a CAF cell line derived from a human SACC and named it CAF-SA. It was identified that CAF-SA expressed typical CAF biomarkers. Then, we studied the cellular communications between CAF-SA, tumor cells and endothelial cells. It was found that CAF-SA promoted the migration, invasion, and proliferation of SACC tumor cells in vitro. In addition, tube formation by endothelial cells was enhanced by CAF-SA. In vivo experiment showed that SACC cells formed larger xenografts in nude mice when they were transplanted with CAF-SA. Overall, we demonstrated that CAF-SA exhibited the most important defining feature of CAF by promoting cancer progression.</p>","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"24 1","pages":"11-18"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15419061.2018.1464000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36076239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-01Epub Date: 2018-09-05DOI: 10.1080/15419061.2018.1493107
Sivakumar Allur Subramaniyan, Sunirmal Sheet, Saravanakumar Balasubramaniam, Swami Vetha Berwin Singh, Dileep Reddy Rampa, Sureshkumar Shanmugam, Da Rae Kang, Ho Sung Choe, Kwan Seob Shim
The objective of this study was to synthesize and characterize novel polyurethane (PU)-nanofiber coated with l-arginine by electrospinning technique. This study determined whether l-arginine conjugated with PU-nanofiber could stimulate cell proliferation and prevent H2O2-induced cell death in satellite cells co-cultured with fibroblasts isolated from Hanwoo (Korean native cattle). Our results showed that l-arginine conjugated with PU nanofiber could reduce cytotoxicity of co-cultured satellite cells. Protein expression levels of bcl-2 were significantly upregulated whereas those of caspase-3 and caspase-7 were significantly downregulated in co-culture of satellite cells compared to those of monoculture cells after treatment with PU-nanofiber coated with l-arginine and which confirmed by Confocal microscope. These results suggest that co-culture of satellite cells with fibroblasts might be able to counter oxidative stress through translocation/penetration of antioxidant, collagen, and molecules secreted to satellite cells. Therefore, this nanofiber might be useful as a wound dressing in animals to counter oxidative stresses.
{"title":"Fabrication of nanofiber coated with l-arginine via electrospinning technique: a novel nanomatrix to counter oxidative stress under crosstalk of co-cultured fibroblasts and satellite cells.","authors":"Sivakumar Allur Subramaniyan, Sunirmal Sheet, Saravanakumar Balasubramaniam, Swami Vetha Berwin Singh, Dileep Reddy Rampa, Sureshkumar Shanmugam, Da Rae Kang, Ho Sung Choe, Kwan Seob Shim","doi":"10.1080/15419061.2018.1493107","DOIUrl":"https://doi.org/10.1080/15419061.2018.1493107","url":null,"abstract":"<p><p>The objective of this study was to synthesize and characterize novel polyurethane (PU)-nanofiber coated with l-arginine by electrospinning technique. This study determined whether l-arginine conjugated with PU-nanofiber could stimulate cell proliferation and prevent H<sub>2</sub>O<sub>2</sub>-induced cell death in satellite cells co-cultured with fibroblasts isolated from Hanwoo (Korean native cattle). Our results showed that l-arginine conjugated with PU nanofiber could reduce cytotoxicity of co-cultured satellite cells. Protein expression levels of bcl-2 were significantly upregulated whereas those of caspase-3 and caspase-7 were significantly downregulated in co-culture of satellite cells compared to those of monoculture cells after treatment with PU-nanofiber coated with l-arginine and which confirmed by Confocal microscope. These results suggest that co-culture of satellite cells with fibroblasts might be able to counter oxidative stress through translocation/penetration of antioxidant, collagen, and molecules secreted to satellite cells. Therefore, this nanofiber might be useful as a wound dressing in animals to counter oxidative stresses.</p>","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"24 1","pages":"19-32"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15419061.2018.1493107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36458333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1080/15419061.2017.1282468
Chuan Yu, Ming Li, Yanan Sun, Xingguo Wang, Yong Chen
Abstract As the initiation step of bacterial infection or biofouling, bacterial adhesion on cells or substrates is generally an optimal target for antibacterial design. Phosphatidylethanolamine (PE) is the principal phospholipid in bacteria, and its function in bacterial adhesion remains unclear. In this study, four E. coli strains including two PE-deficient mutants (PE−PC− and PE−PC+ strains) and two PE-containing wild-type controls (PE + PC− strains) were recruited to investigate the influence of PE deficiency on bacterial adhesion. We found that PE deficiency could impair E. coli adhesion on macrophages (human THP-1-derived and mouse RAW264.7 macrophages) or glass coverslips by downregulating lipopolysaccharide (LPS) biosynthesis, which could be reversible by high galactose/lactose but not glucose cultivation. The data imply that PE play important role in bacterial adhesion probably via affecting LPS biosynthesis and suggest that targeting PE biosynthesis is also a potential antibacterial strategy.
作为细菌感染或生物污垢的起始步骤,细菌在细胞或底物上的粘附通常是抗菌设计的最佳目标。磷脂酰乙醇胺(PE)是细菌体内的主要磷脂,其在细菌黏附中的作用尚不清楚。本研究利用4株大肠杆菌,包括2株PE- PC -和2株PE- PC+突变株和2株含PE的野生型对照(PE + PC -株),研究PE缺乏对细菌黏附的影响。我们发现,PE缺乏可以通过下调脂多糖(LPS)的生物合成来损害大肠杆菌在巨噬细胞(人thp -1来源和小鼠RAW264.7巨噬细胞)或玻璃盖上的粘附,这可以通过高半乳糖/乳糖培养逆转,但葡萄糖培养不可逆转。这些数据表明,PE可能通过影响LPS的生物合成在细菌粘附中发挥重要作用,并提示靶向PE的生物合成也是一种潜在的抗菌策略。
{"title":"Phosphatidylethanolamine Deficiency Impairs Escherichia coli Adhesion by Downregulating Lipopolysaccharide Synthesis, Which is Reversible by High Galactose/Lactose Cultivation","authors":"Chuan Yu, Ming Li, Yanan Sun, Xingguo Wang, Yong Chen","doi":"10.1080/15419061.2017.1282468","DOIUrl":"https://doi.org/10.1080/15419061.2017.1282468","url":null,"abstract":"Abstract As the initiation step of bacterial infection or biofouling, bacterial adhesion on cells or substrates is generally an optimal target for antibacterial design. Phosphatidylethanolamine (PE) is the principal phospholipid in bacteria, and its function in bacterial adhesion remains unclear. In this study, four E. coli strains including two PE-deficient mutants (PE−PC− and PE−PC+ strains) and two PE-containing wild-type controls (PE + PC− strains) were recruited to investigate the influence of PE deficiency on bacterial adhesion. We found that PE deficiency could impair E. coli adhesion on macrophages (human THP-1-derived and mouse RAW264.7 macrophages) or glass coverslips by downregulating lipopolysaccharide (LPS) biosynthesis, which could be reversible by high galactose/lactose but not glucose cultivation. The data imply that PE play important role in bacterial adhesion probably via affecting LPS biosynthesis and suggest that targeting PE biosynthesis is also a potential antibacterial strategy.","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"79 1","pages":"1 - 10"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84109128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1080/15419061.2017.1282469
F. Stierlin, F. Molica, J. Reny, B. Kwak, P. Fontana
Abstract Pannexin1 (Panx1), a membrane channel-forming protein permitting the passage of small-sized molecules, such as ATP, is expressed in human platelets. Recently, we showed that inhibiting Panx1 affects collagen-induced platelet aggregation but not aggregation triggered by other agonists. We also found that a single nucleotide polymorphism (SNP; rs1138800) in the Panx1 gene encoded for a gain-of-function channel (Panx1-400C) and was associated with enhanced collagen-induced platelet reactivity. Here, we assessed the association of this SNP with platelet reactivity in a cohort of 758 stable cardiovascular patients from the ADRIE study treated with aspirin and/or clopidogrel. We found that presence of the Panx1-400C allele was not associated with platelet reactivity in stable cardiovascular patients, irrespective of the platelet aggregation agonist used (collagen, ADP or arachidonic acid) or the anti-platelet drug regimen. Moreover, the Panx1-400A > C SNP did also not affect the re-occurrence of cardiac ischemic events in the same stable cardiovascular patient cohort.
Pannexin1 (Panx1)是一种膜通道形成蛋白,允许小分子(如ATP)通过,在人血小板中表达。最近,我们发现抑制Panx1会影响胶原诱导的血小板聚集,但不会影响其他激动剂引发的血小板聚集。我们还发现单核苷酸多态性(SNP;rs1138800)在Panx1基因中编码一个功能获得通道(Panx1- 400c),并与胶原诱导的血小板反应性增强有关。在这项研究中,我们评估了来自ADRIE研究的758名接受阿司匹林和/或氯吡格雷治疗的稳定心血管患者的SNP与血小板反应性的关系。我们发现,在稳定性心血管患者中,Panx1-400C等位基因的存在与血小板反应性无关,与使用血小板聚集激动剂(胶原蛋白、ADP或花生四烯酸)或抗血小板药物方案无关。此外,Panx1-400A > C SNP也不影响相同稳定心血管患者队列中心脏缺血事件的再发生。
{"title":"Pannexin1 Single Nucleotide Polymorphism and Platelet Reactivity in a Cohort of Cardiovascular Patients","authors":"F. Stierlin, F. Molica, J. Reny, B. Kwak, P. Fontana","doi":"10.1080/15419061.2017.1282469","DOIUrl":"https://doi.org/10.1080/15419061.2017.1282469","url":null,"abstract":"Abstract Pannexin1 (Panx1), a membrane channel-forming protein permitting the passage of small-sized molecules, such as ATP, is expressed in human platelets. Recently, we showed that inhibiting Panx1 affects collagen-induced platelet aggregation but not aggregation triggered by other agonists. We also found that a single nucleotide polymorphism (SNP; rs1138800) in the Panx1 gene encoded for a gain-of-function channel (Panx1-400C) and was associated with enhanced collagen-induced platelet reactivity. Here, we assessed the association of this SNP with platelet reactivity in a cohort of 758 stable cardiovascular patients from the ADRIE study treated with aspirin and/or clopidogrel. We found that presence of the Panx1-400C allele was not associated with platelet reactivity in stable cardiovascular patients, irrespective of the platelet aggregation agonist used (collagen, ADP or arachidonic acid) or the anti-platelet drug regimen. Moreover, the Panx1-400A > C SNP did also not affect the re-occurrence of cardiac ischemic events in the same stable cardiovascular patient cohort.","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"38 1","pages":"11 - 15"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80915062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-02DOI: 10.3109/15419061.2016.1155565
Xiujuan Wang, Kun Liu, Bin Li, Yanning Li, Kaiwei Ye, J. Qi, Yu Wang
Abstract Activated macrophages contribute to endothelial dysfunction; however, it is unclear how peroxynitrite contributes to macrophage-mediated human cardiac microvascular endothelial cell (HCMEC) injury in hypoxia. In macrophage-HCMEC co-cultures subjected to hypoxia, there was an increase in hypoxia-inducible factor (HIF)-1α, HIF-2α, inducible nitric oxide synthase (iNOS), endothelin-converting enzyme (ECE)-1 and cyclooxygenase-2 (COX-2), and concomitant decrease in prostacyclin synthase (PGIS). This was mimicked by a peroxynitrite donor and attenuated by its decomposition catalyst. Tongxinluo (TXL) could decrease HIF-2α, iNOS, ECE-1 and COX-2 and increase PGIS in a dose-dependent manner, with increase of vascular endothelial growth factor. The protein alterations verified the remarkably affected mRNAs, indicating that the effects of TXL were similar to but better than that of peroxynitrite decomposition catalyst. Furthermore, TXL inhibited macrophage-mediated nitrotyrosine accumulation and attenuated HCMEC injury. The results suggest that peroxynitrite contributes to macrophage-mediated HCMEC injury in hypoxia, and TXL attenuates HCMEC injury mainly by inhibiting peroxynitrite.
{"title":"Macrophages Aggravate Hypoxia-Induced Cardiac Microvascular Endothelial Cell Injury via Peroxynitrite: Protection by Tongxinluo","authors":"Xiujuan Wang, Kun Liu, Bin Li, Yanning Li, Kaiwei Ye, J. Qi, Yu Wang","doi":"10.3109/15419061.2016.1155565","DOIUrl":"https://doi.org/10.3109/15419061.2016.1155565","url":null,"abstract":"Abstract Activated macrophages contribute to endothelial dysfunction; however, it is unclear how peroxynitrite contributes to macrophage-mediated human cardiac microvascular endothelial cell (HCMEC) injury in hypoxia. In macrophage-HCMEC co-cultures subjected to hypoxia, there was an increase in hypoxia-inducible factor (HIF)-1α, HIF-2α, inducible nitric oxide synthase (iNOS), endothelin-converting enzyme (ECE)-1 and cyclooxygenase-2 (COX-2), and concomitant decrease in prostacyclin synthase (PGIS). This was mimicked by a peroxynitrite donor and attenuated by its decomposition catalyst. Tongxinluo (TXL) could decrease HIF-2α, iNOS, ECE-1 and COX-2 and increase PGIS in a dose-dependent manner, with increase of vascular endothelial growth factor. The protein alterations verified the remarkably affected mRNAs, indicating that the effects of TXL were similar to but better than that of peroxynitrite decomposition catalyst. Furthermore, TXL inhibited macrophage-mediated nitrotyrosine accumulation and attenuated HCMEC injury. The results suggest that peroxynitrite contributes to macrophage-mediated HCMEC injury in hypoxia, and TXL attenuates HCMEC injury mainly by inhibiting peroxynitrite.","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"1 1","pages":"39 - 47"},"PeriodicalIF":0.0,"publicationDate":"2015-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89120511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-02DOI: 10.3109/15419061.2016.1151875
Joost Willebrords, Sara Crespo Yanguas, M. Maes, E. Decrock, Nan Wang, L. Leybaert, T. C. da Silva, Isabel Veloso Alves Pereira, H. Jaeschke, B. Cogliati, M. Vinken
Abstract Gap junctions are a specialized group of cell-to-cell junctions that mediate direct intercellular communication between cells. They arise from the interaction of two hemichannels of adjacent cells, which in turn are composed of six connexin proteins. In liver, gap junctions are predominantly found in hepatocytes and play critical roles in virtually all phases of the hepatic life cycle, including cell growth, differentiation, liver-specific functionality and cell death. Liver gap junctions are directed through a broad variety of mechanisms ranging from epigenetic control of connexin expression to post-translational regulation of gap junction activity. This paper reviews established and novel aspects regarding the architecture, control and functional relevance of liver gap junctions.
{"title":"Structure, Regulation and Function of Gap Junctions in Liver","authors":"Joost Willebrords, Sara Crespo Yanguas, M. Maes, E. Decrock, Nan Wang, L. Leybaert, T. C. da Silva, Isabel Veloso Alves Pereira, H. Jaeschke, B. Cogliati, M. Vinken","doi":"10.3109/15419061.2016.1151875","DOIUrl":"https://doi.org/10.3109/15419061.2016.1151875","url":null,"abstract":"Abstract Gap junctions are a specialized group of cell-to-cell junctions that mediate direct intercellular communication between cells. They arise from the interaction of two hemichannels of adjacent cells, which in turn are composed of six connexin proteins. In liver, gap junctions are predominantly found in hepatocytes and play critical roles in virtually all phases of the hepatic life cycle, including cell growth, differentiation, liver-specific functionality and cell death. Liver gap junctions are directed through a broad variety of mechanisms ranging from epigenetic control of connexin expression to post-translational regulation of gap junction activity. This paper reviews established and novel aspects regarding the architecture, control and functional relevance of liver gap junctions.","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"169 1","pages":"29 - 37"},"PeriodicalIF":0.0,"publicationDate":"2015-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73931130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-02DOI: 10.1080/15419061.2016.1265949
Sharareh Jalali, M. Tafazzoli-Shadpour, N. Haghighipour, Ramin Omidvar, F. Safshekan
Abstract Although substrate stiffness has been previously reported to affect various cellular aspects, such as morphology, migration, viability, growth, and cytoskeletal structure, its influence on cell adherence has not been well examined. Here, we prepared three soft, medium, and hard polyacrylamide (PAAM) substrates and utilized AFM to study substrate elasticity and also the adhesion and mechanical properties of endothelial cells in response to changing substrate stiffness. Maximum detachment force and cell stiffness were increased with increasing substrate stiffness. Maximum detachment force values were 0.28 ± 0.14, 0.94 ± 0.27, and 1.99 ± 0.59 nN while Young’s moduli of cells were 218.85 ± 38.73, 385.58 ± 131.67, and 933.20 ± 428.92 Pa for soft, medium, and hard substrates, respectively. Human umbilical vein endothelial cells (HUVECs) showed round to more spread shapes on soft to hard substrates, with the most organized and elongated actin structure on the hard hydrogel. Our results confirm the importance of substrate stiffness in regulating cell mechanics and adhesion for a successful cell therapy.
{"title":"Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness","authors":"Sharareh Jalali, M. Tafazzoli-Shadpour, N. Haghighipour, Ramin Omidvar, F. Safshekan","doi":"10.1080/15419061.2016.1265949","DOIUrl":"https://doi.org/10.1080/15419061.2016.1265949","url":null,"abstract":"Abstract Although substrate stiffness has been previously reported to affect various cellular aspects, such as morphology, migration, viability, growth, and cytoskeletal structure, its influence on cell adherence has not been well examined. Here, we prepared three soft, medium, and hard polyacrylamide (PAAM) substrates and utilized AFM to study substrate elasticity and also the adhesion and mechanical properties of endothelial cells in response to changing substrate stiffness. Maximum detachment force and cell stiffness were increased with increasing substrate stiffness. Maximum detachment force values were 0.28 ± 0.14, 0.94 ± 0.27, and 1.99 ± 0.59 nN while Young’s moduli of cells were 218.85 ± 38.73, 385.58 ± 131.67, and 933.20 ± 428.92 Pa for soft, medium, and hard substrates, respectively. Human umbilical vein endothelial cells (HUVECs) showed round to more spread shapes on soft to hard substrates, with the most organized and elongated actin structure on the hard hydrogel. Our results confirm the importance of substrate stiffness in regulating cell mechanics and adhesion for a successful cell therapy.","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"2011 1","pages":"79 - 89"},"PeriodicalIF":0.0,"publicationDate":"2015-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86324127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-04-01Epub Date: 2016-09-07DOI: 10.1080/15419061.2016.1223634
Dorothea Fischbacher, Marion Merle, Anja Liepert, Christine Grabrucker, Tanja Kroell, Andreas Kremser, Julia Dreyßig, Markus Freudenreich, Friedhelm Schuster, Arndt Borkhardt, Doris Kraemer, Claus-Henning Koehne, Hans-Jochem Kolb, Christoph Schmid, Helga Maria Schmetzer
To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.
{"title":"Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients' Response to Immunotherapy.","authors":"Dorothea Fischbacher, Marion Merle, Anja Liepert, Christine Grabrucker, Tanja Kroell, Andreas Kremser, Julia Dreyßig, Markus Freudenreich, Friedhelm Schuster, Arndt Borkhardt, Doris Kraemer, Claus-Henning Koehne, Hans-Jochem Kolb, Christoph Schmid, Helga Maria Schmetzer","doi":"10.1080/15419061.2016.1223634","DOIUrl":"https://doi.org/10.1080/15419061.2016.1223634","url":null,"abstract":"<p><p>To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.</p>","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"22 2-6","pages":"49-65"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15419061.2016.1223634","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34424282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-04-01Epub Date: 2016-09-07DOI: 10.1080/15419061.2016.1225196
Mi-Hyun Nam, Won-Rak Son, Young Sik Lee, Kwang-Won Lee
Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.
{"title":"Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.","authors":"Mi-Hyun Nam, Won-Rak Son, Young Sik Lee, Kwang-Won Lee","doi":"10.1080/15419061.2016.1225196","DOIUrl":"https://doi.org/10.1080/15419061.2016.1225196","url":null,"abstract":"<p><p>Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.</p>","PeriodicalId":55269,"journal":{"name":"Cell Communication and Adhesion","volume":"22 2-6","pages":"67-78"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15419061.2016.1225196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34726993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}