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{"title"=>"Dynorphin 1-17 and its n-terminal biotransformation fragments modulate lipopolysaccharide-stimulated nuclear factor-kappa b nuclear translocation, interleukin-1beta and tumor necrosis factoralpha in differentiated THP-1 cells", "type"=>"journal", "authors"=>[{"first_name"=>"Siti Sarah Fazalul", "last_name"=>"Rahiman", "scopus_author_id"=>"57188841076"}, {"first_name"=>"Michael", "last_name"=>"Morgan", "scopus_author_id"=>"57054753100"}, {"first_name"=>"Paul", "last_name"=>"Gray", "scopus_author_id"=>"19234338500"}, {"first_name"=>"Paul Nicholas", "last_name"=>"Shaw", "scopus_author_id"=>"7401650163"}, {"first_name"=>"Peter John", "last_name"=>"Cabot", "scopus_author_id"=>"35553526700"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84963779758", "doi"=>"10.1371/journal.pone.0153005", "sgr"=>"84963779758", "pui"=>"609703231"}, "id"=>"3bfad597-6259-3886-9e03-8a9a5cf82bfd", "link"=>"http://www.mendeley.com/research/dynorphin-117-nterminal-biotransformation-fragments-modulate-lipopolysaccharidestimulated-nuclear-fa", "reader_count"=>5, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>0}

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• http://doi.org/10.1016/j.peptides.2017.02.004
• http://doi.org/10.1016/j.peptides.2018.01.011
• http://doi.org/10.1186/s12906-019-2574-9
• http://doi.org/10.1016/j.peptides.2016.12.019

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• {"id"=>"890437544311222273", "text"=>"Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulate ... https://t.co/vnSG0Kj019", "created_at"=>"2017-07-27T05:03:48Z", "user"=>"Oxyconmdamu", "user_name"=>"Bearzapine,PharmC", "user_profile_image"=>"http://pbs.twimg.com/profile_images/868633428039696384/r6y1mReb_normal.jpg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/4929226"], "description"=>"<p>The LPS-stimulated THP-1 cells were treated with the N-terminal fragments of DYN 1–17 and U50,488H at 0.1 μM, 1 nM and 10 pM for 24 hr. The culture supernatants were collected and IL-1β and TNF-α release was measured using IL-1β and TNF-α AlphaLISA kit, respectively. The AlphaLISA signal was read using an Enspire-Alpha 2390 Multilabel Plate Reader. Non-stimulated THP-1 cells (NS) served as negative control. The release of IL-1β and TNF-α in each treatment group was normalised and expressed relative to LPS-stimulated control group. Data shown are the means ± S.E.M. of at least three independent experiments performed in triplicates. Statistical significance as denoted by * and # represent the IL-1β and TNF-α release between peptide-treated (solid-line) and LPS-stimulated control group or ML-190-treated group (dotted-line), respectively, p ≤ 0.05.</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165571, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_modulation_of_DYN_1_17_and_the_N_terminal_fragments_on_the_release_of_IL_1_and_TNF_in_LPS_stimulated_THP_1_cells_/3165571", "title"=>"The modulation of DYN 1–17 and the N-terminal fragments on the release of IL-1β and TNF-α in LPS-stimulated THP-1 cells.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929187"], "description"=>"<p>The LPS-stimulated THP-1 cells were pre-treated with ML-190, a KOP receptor antagonist (1 μM, 1 hour) followed by co-treatment of the DYN 1–17 and the N-terminal fragments (10 nM) or U50,488H (10 nM) with ML-190 (1 μM, 1 hour). The treated cells were fixed with paraformaldehyde (3.7%) and immunolabelled with primary anti-NF-κB/p65 rabbit monoclonal antibody and visualized using Alexa Fluor 555^® secondary antibody. DAPI staining was used to identify the nuclei. The nuclear translocation of NF-κB/p65 in each treatment group was assessed using the Image Xpress system. Non-stimulated THP-1 cells (NS) served as negative control. The percentage of NF-κB/p65 nuclear translocation in each treatment group was normalised and expressed relative to LPS-stimulated control group (contains DMSO 0.1% as diluent control). Data shown are the means ± S.E.M. of at least three independent experiments performed in triplicates, *p ≤ 0.05.</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165541, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_ML_190_on_the_attenuation_of_NF_B_p65_nuclear_translocation_by_DYN_1_17_and_the_N_terminal_fragments_in_LPS_stimulated_THP_1_cells_/3165541", "title"=>"Effect of ML-190 on the attenuation of NF-κB/p65 nuclear translocation by DYN 1–17 and the N-terminal fragments in LPS-stimulated THP-1 cells.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929157"], "description"=>"<p>Cells were fixed, permeabilised, immunolabelled with KOP receptor monoclonal antibody and visualised with Alexa Fluor 647^® goat anti-mouse IgG (red). The nuclei were counterstained with DAPI (blue). Images were acquired for each fluorescence channel, using suitable FITC and DAPI filters with 20 × objective. Scale bar: 25μm</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165514, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_expression_of_KOP_receptor_on_LPS_stimulated_THP_1_cells_/3165514", "title"=>"The expression of KOP receptor on LPS-stimulated THP-1 cells.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929001", "https://ndownloader.figshare.com/files/4929010", "https://ndownloader.figshare.com/files/4929016", "https://ndownloader.figshare.com/files/4929022", "https://ndownloader.figshare.com/files/4929034"], "description"=>"<div><p>Dynorphin 1–17, (DYN 1–17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1–17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1–17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) from lipopolysaccharide (LPS)-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1–17 and a specific range of fragments, with the greatest reduction observed with DYN 1–7 at a low concentration (10 nM). Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1–17, DYN 1–6, DYN 1–7 and DYN 1–9, but not other DYN 1–17 N-terminal fragments (DYN 1–10 and 1–11) on NF-κB/p65 nuclear translocation. DYN 1–17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1–7 at low concentrations (1 nM and 10 pM). These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1–17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.</p></div>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165388, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0153005.s001", "https://dx.doi.org/10.1371/journal.pone.0153005.s002", "https://dx.doi.org/10.1371/journal.pone.0153005.s003", "https://dx.doi.org/10.1371/journal.pone.0153005.s004", "https://dx.doi.org/10.1371/journal.pone.0153005.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dynorphin_1_17_and_Its_N_Terminal_Biotransformation_Fragments_Modulate_Lipopolysaccharide_Stimulated_Nuclear_Factor_kappa_B_Nuclear_Translocation_Interleukin_1beta_and_Tumor_Necrosis_Factor_alpha_in_Differentiated_THP_1_Cells/3165388", "title"=>"Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929133"], "description"=>"<p>The LPS-stimulated THP-1 cells were treated with IMD-0354 (10 μM) and DMSO (0.1% v/v, as diluent control). The treated cells were fixed with paraformaldehyde (3.7%) and immunolabelled with primary anti-NF-κB/p65 rabbit monoclonal antibody and visualized using Alexa Fluor 555^® secondary antibody. DAPI staining was used to identify the nuclei. The nuclear translocation of NF-κB/p65 in each treatment group was assessed using the Image Xpress system. Non-stimulated THP-1 cells (NS), receiving similar treatment served as negative control. The percentage of NF-κB/p65 nuclear translocation in each treatment group was normalised and expressed relative to LPS-stimulated control group. Data represents means ± S.E.M. of at least three independent experiments performed in triplicates, *p ≤ 0.05.</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165487, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_IMD_0354_on_the_NF_B_p65_nuclear_translocation_in_LPS_stimulated_THP_1_cells_/3165487", "title"=>"Effect of IMD-0354 on the NF-κB/p65 nuclear translocation in LPS-stimulated THP-1 cells.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929079"], "description"=>"<p>Cells were fixed, permeabilised, stained with anti-NF-κB/p65 rabbit monoclonal antibody and visualised with Alexa Fluor^® 555 goat anti-rabbit IgG (green). The nuclei were counterstained with DAPI (blue). Microscopy images <b>A.</b> Inactive NF-κB/p65 proteins localisation in the cytoplasm of the non-stimulated THP-1 cells (top row) and <b>B.</b> Translocated NF-κB/p65 proteins into the nuclei of THP-1 cells following LPS stimulation (bottom row). Images were acquired for each fluorescence channel, using suitable TRITC and DAPI filters and a 63× objective. Scale bar: 10μm</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165433, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/NF_B_p65_nuclear_localisation_in_differentiated_THP_1_cells_/3165433", "title"=>"NF-κB/p65 nuclear localisation in differentiated THP-1 cells.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929103"], "description"=>"<p>The LPS-stimulated THP-1 cells were treated with the N-terminal fragments of DYN 1–17 and U50,488H at 1 μM and 10 nM for an hour. The treated cells were fixed with paraformaldehyde (3.7%) and immunolabelled with primary anti-NF-κB/p65 monoclonal antibody and visualized using Alexa Fluor 555^® secondary antibody. DAPI staining was used to identify the nuclei. The nuclear translocation of NF-κB/p65 in each treatment group was assessed using the Image Xpress screening system. Non-stimulated THP-1 cells (NS) served as negative control. The NF-κB/p65 translocation percentage in each treatment group was normalised and expressed relative to LPS-stimulated control group. Data shown are the means ± S.E.M. of at least three independent experiments performed in triplicates, *p ≤ 0.05.</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165466, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_attenuation_of_NF_B_p65_nuclear_translocation_by_DYN_1_17_and_the_N_terminal_fragments_in_LPS_stimulated_THP_1_cells_/3165466", "title"=>"The attenuation of NF-κB/p65 nuclear translocation by DYN 1–17 and the N-terminal fragments in LPS-stimulated THP-1 cells.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-07 05:23:35"}
• {"files"=>["https://ndownloader.figshare.com/files/4929250"], "description"=>"<p>The Effects of DYN 1–17 and Its N-terminal Biotransformation Fragments on LPS-stimulated NF-κB/p65 nuclear translocation.</p>", "links"=>[], "tags"=>["fragment", "LPS", "Differentiated THP", "ML", "NF", "KOP receptor antagonist", "cytokine release", "DYN", "immunomodulatory effects", "10 pM", "TNF", "IL"], "article_id"=>3165595, "categories"=>["Biochemistry", "Space Science", "Microbiology", "Cell Biology", "Neuroscience", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Cancer"], "users"=>["Siti Sarah Fazalul Rahiman", "Michael Morgan", "Paul Gray", "Paul Nicholas Shaw", "Peter John Cabot"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153005.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Effects_of_DYN_1_17_and_Its_N_terminal_Biotransformation_Fragments_on_LPS_stimulated_NF_B_p65_nuclear_translocation_/3165595", "title"=>"The Effects of DYN 1–17 and Its N-terminal Biotransformation Fragments on LPS-stimulated NF-κB/p65 nuclear translocation.", "pos_in_sequence"=>8, "defined_type"=>3, "published_date"=>"2016-04-07 05:23:35"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}

F1000Prime