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Tilman Sanchezelsner - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 31 and microRNA 155 are overexpressed in ulcerative colitis and regulate il 13 signaling by targeting interleukin 13 receptor α 1
    Genes, 2018
    Co-Authors: Markus Gwiggner, Rocio T Martineznunez, Simon R Whiteoak, Victor P Bondanese, Andrew Claridge, Jane E Collins, J Fraser R Cummings, Tilman Sanchezelsner
    Abstract:

    Interleukin-13 (IL-13) is an important Type 2 T helper (Th2) cytokine, controlling biological functions in epithelium and has been linked to asthma, atopic dermatitis and ulcerative colitis (UC). Interleukin-13 signals through IL-13 receptor α-1 (IL13RA1 (gene) and IL13Rα1 (protein)), a receptor that can be regulated by microRNAs (miRs). microRNAs are small non-coding single-stranded RNAs with a role in several pathologies. However, their relevance in the pathophysiology of UC, a chronic inflammatory condition of the colonic mucosa, is poorly characterised. Here, we determined the expression of IL13Rα1 in UC, its potential regulation by miRs and the subsequent effect on IL-13 signalling. Inflamed mucosa of UC patients showed decreased mRNA and protein expression of IL13RA1 when compared to healthy controls. We show that miR-31 and miR-155 are upregulated in inflamed UC mucosa and that both directly target the 3′ untranslated region of IL13RA1 mRNA. Transfection of miR-31 and miR-155 mimics reduced the expression of IL13RA1 mRNA and protein, and blocked IL-13-dependent phosphorylation of signal transducer and activator of transcription 6 (STAT6) in HT-29 cells, a gut epithelium cell line. Interleukin-13 activation of suppressor of cytokine signaling 1 (SOCS1) and eotaxin-3 (CCL26) expression was also diminished. microRNA-31/microRNA-155 mimics also downregulated IL13RA1 in ex vivo human inflamed UC biopsies. We propose that miR-31 and miR-155 have an important role in limiting IL-13 signalling in UC disease.

  • the interleukin 13 il 13 pathway in human macrophages is modulated by microRNA 155 via direct targeting of interleukin 13 receptor α1 il13rα1
    Journal of Biological Chemistry, 2011
    Co-Authors: Rocio T Martineznunez, Fethi Louafi, Tilman Sanchezelsner
    Abstract:

    Macrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th1) and M2 (alternative, pro-Th2) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th2 cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor α1 (IL13Rα1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. microRNAs are short (∼22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13Rα1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th1/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13Rα1 and reduces the levels of IL13Rα1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th2 phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages.

  • microRNA 155 modulates the pathogen binding ability of dendritic cells dcs by down regulation of dc specific intercellular adhesion molecule 3 grabbing non integrin dc sign
    Journal of Biological Chemistry, 2009
    Co-Authors: Rocio T Martineznunez, Tilman Sanchezelsner, Fethi Louafi, Peter S Friedmann
    Abstract:

    microRNA-155 (miR-155) has been involved in the response to inflammation in macrophages and lymphocytes. Here we show how miR-155 participates in the maturation of human dendritic cells (DC) and modulates pathogen binding by down-regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), after directly targeting the transcription factor PU.1. During the maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels decrease accordingly. We establish that human PU.1 is a direct target for miR-155 and localize the target sequence for miR-155 in the 3′-untranslated region of PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a link between the down-regulation of PU.1 and reduced transcriptional activity of the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA expression, after miR-155 overexpression. Finally, we show that, by reducing DC-SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding as dendritic cells exhibited the lower binding capacity for fungi and HIV protein gp-120 when the levels of miR-155 were higher. Thus, our results suggest a mechanism by which miR-155 regulates proteins involved in the cellular immune response against pathogens that could have clinical implications in the way pathogens enter the human organism.

Rocio T Martineznunez - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 31 and microRNA 155 are overexpressed in ulcerative colitis and regulate il 13 signaling by targeting interleukin 13 receptor α 1
    Genes, 2018
    Co-Authors: Markus Gwiggner, Rocio T Martineznunez, Simon R Whiteoak, Victor P Bondanese, Andrew Claridge, Jane E Collins, J Fraser R Cummings, Tilman Sanchezelsner
    Abstract:

    Interleukin-13 (IL-13) is an important Type 2 T helper (Th2) cytokine, controlling biological functions in epithelium and has been linked to asthma, atopic dermatitis and ulcerative colitis (UC). Interleukin-13 signals through IL-13 receptor α-1 (IL13RA1 (gene) and IL13Rα1 (protein)), a receptor that can be regulated by microRNAs (miRs). microRNAs are small non-coding single-stranded RNAs with a role in several pathologies. However, their relevance in the pathophysiology of UC, a chronic inflammatory condition of the colonic mucosa, is poorly characterised. Here, we determined the expression of IL13Rα1 in UC, its potential regulation by miRs and the subsequent effect on IL-13 signalling. Inflamed mucosa of UC patients showed decreased mRNA and protein expression of IL13RA1 when compared to healthy controls. We show that miR-31 and miR-155 are upregulated in inflamed UC mucosa and that both directly target the 3′ untranslated region of IL13RA1 mRNA. Transfection of miR-31 and miR-155 mimics reduced the expression of IL13RA1 mRNA and protein, and blocked IL-13-dependent phosphorylation of signal transducer and activator of transcription 6 (STAT6) in HT-29 cells, a gut epithelium cell line. Interleukin-13 activation of suppressor of cytokine signaling 1 (SOCS1) and eotaxin-3 (CCL26) expression was also diminished. microRNA-31/microRNA-155 mimics also downregulated IL13RA1 in ex vivo human inflamed UC biopsies. We propose that miR-31 and miR-155 have an important role in limiting IL-13 signalling in UC disease.

  • the interleukin 13 il 13 pathway in human macrophages is modulated by microRNA 155 via direct targeting of interleukin 13 receptor α1 il13rα1
    Journal of Biological Chemistry, 2011
    Co-Authors: Rocio T Martineznunez, Fethi Louafi, Tilman Sanchezelsner
    Abstract:

    Macrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th1) and M2 (alternative, pro-Th2) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th2 cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor α1 (IL13Rα1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. microRNAs are short (∼22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13Rα1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th1/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13Rα1 and reduces the levels of IL13Rα1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th2 phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages.

  • microRNA 155 modulates the pathogen binding ability of dendritic cells dcs by down regulation of dc specific intercellular adhesion molecule 3 grabbing non integrin dc sign
    Journal of Biological Chemistry, 2009
    Co-Authors: Rocio T Martineznunez, Tilman Sanchezelsner, Fethi Louafi, Peter S Friedmann
    Abstract:

    microRNA-155 (miR-155) has been involved in the response to inflammation in macrophages and lymphocytes. Here we show how miR-155 participates in the maturation of human dendritic cells (DC) and modulates pathogen binding by down-regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), after directly targeting the transcription factor PU.1. During the maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels decrease accordingly. We establish that human PU.1 is a direct target for miR-155 and localize the target sequence for miR-155 in the 3′-untranslated region of PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a link between the down-regulation of PU.1 and reduced transcriptional activity of the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA expression, after miR-155 overexpression. Finally, we show that, by reducing DC-SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding as dendritic cells exhibited the lower binding capacity for fungi and HIV protein gp-120 when the levels of miR-155 were higher. Thus, our results suggest a mechanism by which miR-155 regulates proteins involved in the cellular immune response against pathogens that could have clinical implications in the way pathogens enter the human organism.

Mohammad Reza Ganjali - One of the best experts on this subject based on the ideXlab platform.

  • label free fluorescent detection of microRNA 155 based on synthesis of hairpin dna templated copper nanoclusters by etching top down approach
    Sensors and Actuators B-chemical, 2017
    Co-Authors: Yasamansadat Borghei, Morteza Hosseini, Mohammad Reza Ganjali, Saman Hosseinkhani
    Abstract:

    Abstract In this study, we have reported a new approach for sequence specific microRNA-155 (miRNA-155) detection by water soluble luminescent copper nanoclusters. The method is based on the shifts in the fluorescence emissions of oligonucleotide-templated copper nanoclusters (DNA-CuNCs) and can be regarded as the first instance of using fluorescent CuNCs for the detection of microRNA by forming DNA-RNA heteroduplex. The as-prepared CuNCs exhibited a strong fluorescence enhancement at 510 nm and a red shift (60 nm) when bonded to the target miRNA-155 (DNA-RNA heteroduplex formation). Under the optimal conditions, the fluorescent intensity of DNA-CuNCs increased by the increasing the target miRNA-155 with in a dynamic range from 5.0 × 10 −12 to 1.0 × 10 −8  M down to a detection limit (LOD) of 2.2 × 10 −12  M. The target miRNA is selectively discriminated from mismatched miRNA by this method. The method was further applied to the determination of miRNA spiked human serum samples. Overall, the nanobiosensor showed the potential of becoming a potential alternative tool for the detection of miRNA-155 in biomedical research and early clinical diagnostic studies.

  • fluorescence based turn on strategy for determination of microRNA 155 using dna templated copper nanoclusters
    Mikrochimica Acta, 2017
    Co-Authors: Yasamansadat Borghei, Morteza Hosseini, Mohammad Reza Ganjali
    Abstract:

    The authors report on a new approach for the determination of the breast cancer biomarker microRNA-155 (miRNA-155). It is based on the measurement of the fluorescence shift of oligonucleotide-templated copper nanoclusters (DNA-CuNC). A probe DNA was designed that acts as a template for the preparation of CuNC which, under 400 nm excitation, exhibit strong fluorescence enhancement at 490 nm and a 90 nm Stokes shift after binding to target miRNA-155 and formation of a DNA-RNA heteroduplex. Under the optimal conditions, the fluorescence of the DNA-CuNC increases with increasing concentration of miRNA-155 in the range from 50 pM to 10 nM, with a 11 pM detection limit. The assay has excellent selectivity over noncomplementary RNA. The method was applied to the determination of miRNA-155 in the presence of human plasma and saliva.

Parvathi Ranganathan - One of the best experts on this subject based on the ideXlab platform.

  • microRNA 155 modulates acute graft versus host disease by impacting t cell expansion migration and effector function
    Journal of Immunology, 2018
    Co-Authors: Nina C Zitzer, Patricia A Taylor, Katiri Snyder, Xiamoei Meng, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Ramiro Garzon, Parvathi Ranganathan
    Abstract:

    microRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155-deficient (miR155-/-) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated. We identify that miR-155 expression in both donor CD8+ T cells and conventional CD4+ CD25- T cells is pivotal for aGVHD pathogenesis. Using murine aGVHD transplant experiments, we show that miR-155 strongly impacts alloreactive T cell expansion through multiple distinct mechanisms, modulating proliferation in CD8+ donor T cells and promoting exhaustion in donor CD4+ T cells in both the spleen and colon. Additionally, miR-155 drives a proinflammatory Th1 phenotype in donor T cells in these two sites, and miR-155-/- donor T cells are polarized toward an IL-4-producing Th2 phenotype. We further demonstrate that miR-155 expression in donor T cells regulates CCR5 and CXCR4 chemokine-dependent migration. Notably, we show that miR-155 expression is crucial for donor T cell infiltration into multiple target organs. These findings provide further understanding of the role of miR-155 in modulating aGVHD through T cell expansion, effector cytokine production, and migration.

  • regulation of acute graft versus host disease by microRNA 155
    Blood, 2010
    Co-Authors: Parvathi Ranganathan, Catherine E A Heaphy, Stefan Costinean, Nicole Stauffer, Caroline Na, Mehdi Hamadani, Ramasamy Santhanam, Patricia A Taylor, Sukhinder K Sandhu, Gang He
    Abstract:

    Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need to further elucidate its mechanisms and develop novel treatments. Based on recent observations that microRNA-155 (miR-155) is up-regulated during T-cell activation, we hypothesized that miR-155 is involved in the modulation of aGVHD. Here we show that miR-155 expression was up-regulated in T cells from mice developing aGVHD after alloHSCT. Mice receiving miR-155–deficient donor lymphocytes had markedly reduced lethal aGVHD, whereas lethal aGVHD developed rapidly in mice recipients of miR-155 overexpressing T cells. Blocking miR-155 expression using a synthetic anti–miR-155 after alloHSCT decreased aGVHD severity and prolonged survival in mice. Finally, miR-155 up-regulation was shown in specimens from patients with pathologic evidence of intestinal aGVHD. Altogether, our data indicate a role for miR-155 in the regulation of GVHD and point to miR-155 as a novel target for therapeutic intervention in this disease.

Morteza Hosseini - One of the best experts on this subject based on the ideXlab platform.

  • label free fluorescent detection of microRNA 155 based on synthesis of hairpin dna templated copper nanoclusters by etching top down approach
    Sensors and Actuators B-chemical, 2017
    Co-Authors: Yasamansadat Borghei, Morteza Hosseini, Mohammad Reza Ganjali, Saman Hosseinkhani
    Abstract:

    Abstract In this study, we have reported a new approach for sequence specific microRNA-155 (miRNA-155) detection by water soluble luminescent copper nanoclusters. The method is based on the shifts in the fluorescence emissions of oligonucleotide-templated copper nanoclusters (DNA-CuNCs) and can be regarded as the first instance of using fluorescent CuNCs for the detection of microRNA by forming DNA-RNA heteroduplex. The as-prepared CuNCs exhibited a strong fluorescence enhancement at 510 nm and a red shift (60 nm) when bonded to the target miRNA-155 (DNA-RNA heteroduplex formation). Under the optimal conditions, the fluorescent intensity of DNA-CuNCs increased by the increasing the target miRNA-155 with in a dynamic range from 5.0 × 10 −12 to 1.0 × 10 −8  M down to a detection limit (LOD) of 2.2 × 10 −12  M. The target miRNA is selectively discriminated from mismatched miRNA by this method. The method was further applied to the determination of miRNA spiked human serum samples. Overall, the nanobiosensor showed the potential of becoming a potential alternative tool for the detection of miRNA-155 in biomedical research and early clinical diagnostic studies.

  • fluorescence based turn on strategy for determination of microRNA 155 using dna templated copper nanoclusters
    Mikrochimica Acta, 2017
    Co-Authors: Yasamansadat Borghei, Morteza Hosseini, Mohammad Reza Ganjali
    Abstract:

    The authors report on a new approach for the determination of the breast cancer biomarker microRNA-155 (miRNA-155). It is based on the measurement of the fluorescence shift of oligonucleotide-templated copper nanoclusters (DNA-CuNC). A probe DNA was designed that acts as a template for the preparation of CuNC which, under 400 nm excitation, exhibit strong fluorescence enhancement at 490 nm and a 90 nm Stokes shift after binding to target miRNA-155 and formation of a DNA-RNA heteroduplex. Under the optimal conditions, the fluorescence of the DNA-CuNC increases with increasing concentration of miRNA-155 in the range from 50 pM to 10 nM, with a 11 pM detection limit. The assay has excellent selectivity over noncomplementary RNA. The method was applied to the determination of miRNA-155 in the presence of human plasma and saliva.