A p38 MAPK-Mediated Alteration of COX-2/PGE2 Regulates Immunomodulatory Properties in Human Mesenchymal Stem Cell Aging
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"A p38 MAPK-Mediated Alteration of COX-2/PGE2 Regulates Immunomodulatory Properties in Human Mesenchymal Stem Cell Aging", "type"=>"journal", "authors"=>[{"first_name"=>"Kyung-Rok", "last_name"=>"Yu"}, {"first_name"=>"Jin Young", "last_name"=>"Lee"}, {"first_name"=>"Hyung-Sik", "last_name"=>"Kim"}, {"first_name"=>"In-Sun", "last_name"=>"Hong"}, {"first_name"=>"Soon Won", "last_name"=>"Choi"}, {"first_name"=>"Yoojin", "last_name"=>"Seo"}, {"first_name"=>"Insung", "last_name"=>"Kang"}, {"first_name"=>"Jae-Jun", "last_name"=>"Kim"}, {"first_name"=>"Byung-Chul", "last_name"=>"Lee"}, {"first_name"=>"SeungHee", "last_name"=>"Lee"}, {"first_name"=>"Andreas", "last_name"=>"Kurtz"}, {"first_name"=>"Kwang-Won", "last_name"=>"Seo"}, {"first_name"=>"Kyung-Sun", "last_name"=>"Kang"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84905472517", "doi"=>"10.1371/journal.pone.0102426", "pui"=>"373700510", "pmid"=>"25090227", "issn"=>"1932-6203", "isbn"=>"1932-6203"}, "id"=>"25518478-8f55-3fc1-9821-4a7b69e2cd72", "abstract"=>"Because human mesenchymal stem cells (hMSC) have profound immunomodulatory effects, many attempts have been made to use hMSCs in preclinical and clinical trials. For hMSCs to be used in therapy, a large population of hMSCs must be generated by in vitro expansion. However, the immunomodulatory changes following the in vitro expansion of hMSCs have not been elucidated. In this study, we evaluated the effect of replicative senescence on the immunomodulatory ability of hMSCs in vitro and in vivo. Late-passage hMSCs showed impaired suppressive effect on mitogen-induced mononuclear cell proliferation. Strikingly, late-passage hMSCs had a significantly compromised protective effect against mouse experimental colitis, which was confirmed by gross and histologic examination. Among the anti-inflammatory cytokines, the production of prostaglandin E2 (PGE2) and the expression of its primary enzyme, cyclooxygenase-2 (COX-2), were profoundly increased by pre-stimulation with interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), and this response was significantly decreased with consecutive passages. We demonstrated that the impaired phosphorylation activity of p38 MAP kinase (p38 MAPK) in late-passage hMSCs led to a compromised immunomodulatory ability through the regulation of COX-2. In conclusion, our data indicate that the immunomodulatory ability of hMSCs gradually declines with consecutive passages via a p38-mediated alteration of COX-2 and PGE2 levels.", "link"=>"http://www.mendeley.com/research/p38-mapkmediated-alteration-cox2pge2-regulates-immunomodulatory-properties-human-mesenchymal-stem-ce-2", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>6, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>6, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>5, "Social Sciences"=>1, "Immunology and Microbiology"=>1, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84905472517"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84905472517?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84905472517&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84905472517&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84905472517", "dc:identifier"=>"SCOPUS_ID:84905472517", "eid"=>"2-s2.0-84905472517", "dc:title"=>"A p38 MAPK-mediated alteration of COX-2/PGE2 regulates immunomodulatory properties in human mesenchymal stem cell aging", "dc:creator"=>"Yu K.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"8", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-08-04", "prism:coverDisplayDate"=>"4 August 2014", "prism:doi"=>"10.1371/journal.pone.0102426", "citedby-count"=>"27", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Seoul National University", "affiliation-city"=>"Seoul", "affiliation-country"=>"South Korea"}], "pubmed-id"=>"25090227", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e102426", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0102426", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"86", "xml_views"=>"20", "html_views"=>"415"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"81"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"81"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"31", "xml_views"=>"2", "html_views"=>"73"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"62"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"46"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"53"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"36", "xml_views"=>"1", "html_views"=>"49"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"3", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"25", "xml_views"=>"2", "html_views"=>"47"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"19"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"10"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"15"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"6"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1620465"], "description"=>"<p>(A–C) Images of differentiated hMSCs after induction into specific tissues. (A) The lipid droplet accumulation in differentiated cells was visualized using Oil Red O staining after 2 weeks of adipogenic induction. (B) Calcium deposition was stained with Alizarin Red S after 2 weeks of osteogenic induction. (C) Glycosaminoglycans in cell pellets were revealed by Toluidine blue staining after 2 weeks of chondrogenic induction. (D) hMSCs (1×10<sup>6</sup> cells/ml) were stained with FITC- or PE- conjugated antibodies specific for human CD29, CD34, CD45, CD73, CD105, and HLA-DR.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression"], "article_id"=>1126482, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_hMSCs_/1126482", "title"=>"Characterization of hMSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-04 02:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1620478"], "description"=>"<p>(A) Phase contrast images of early- and late-passage hMSCs. β-gal staining was performed in the early-passage and late-passage hMSCs to confirm their senescence. (B) The cumulative population doubling levels of hMSCs were calculated after each repeated subculture to evaluate the loss of their proliferation potential. n = 3. (**<i>P</i><0.01). (C, D) hMNCs were treated with Concanavalin A to stimulate proliferation and colony formation. Stimulated hMNCs were co-cultured with early- or late-passage hMSCs at a 1∶10 ratio (MSC:MNC). White arrows indicate colonies of MNCs (C). hMNC proliferation was assessed after 72 hours using a BrdU kit (D). The results show four representative results from experiments using three different hMSC lines. Scale bar  = 100 µm. n = 3. (**<i>P</i><0.01). (E, F) Human primary T cell proliferation was induced by treatment of anti-CD3 monoclonal antibody, anti-CD28 monoclonal antibody and IL-2 to hMNCs. Activated human T cells were co-cultured with early- or late-passage hMSCs at a 1∶10 ratio (MSC:MNC) (E). T cell proliferation was measured by BrdU assay after 72 hours (F). The graph shows two representative results from experiments using three different hMSC lines. Scale bar  = 100 µm. n = 3. (**P<0.01).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression", "senescent", "hmscs", "impaired", "immunosuppressive"], "article_id"=>1126495, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replicative_senescent_hMSCs_show_impaired_immunosuppressive_ability_/1126495", "title"=>"Replicative senescent hMSCs show impaired immunosuppressive ability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-04 02:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1620490"], "description"=>"<p>(A–F) 3% DSS water was administered to mice for seven days to induce colitis. Early- or late-passage hMSCs were injected intraperitoneally one day after the administration of DSS. The percentage of body weight loss (A), the Mantel Cox analysis of survival rate (B) and the disease activity index for colitis severity (C) were monitored as clinical progression. Mice were sacrificed ten days after the induction of colitis with DSS, and the length (D), weight-to-length ratios of the colons (E) and colon sections were stained with H&E and histopathologic evaluation was investigated by determining lymphocyte infiltration and intestinal damage (F, G). (*<i>P</i><0.05, **<i>P</i><0.01).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression", "late-passage", "hmscs", "dss-induced", "colitis"], "article_id"=>1126499, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Administration_of_late_passage_hMSCs_reduces_the_protective_effects_against_DSS_induced_colitis_in_mice_/1126499", "title"=>"Administration of late-passage hMSCs reduces the protective effects against DSS-induced colitis in mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-04 02:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1620504"], "description"=>"<p>(A–E) Early- and late-passage hMSCs were treated with or without IFN-γ and TNF-α for 24 hours. (A, D) The PGE<sub>2</sub> concentration was measured from the culture supernatant by an ELISA after IFN-γ and TNF-α treatment for 24 hours. n = 3. (**<i>P</i><0.01) (B, C, E) COX-2 expression was investigated using Western blot and immunocytochemistry after exposure to IFN-γ and TNF-α for 24 hours. GAPDH was used for normalization. n = 3. (**<i>P</i><0.01) (F) Concanavalin A stimulated hMNCs were cultured alone or co-cultured with early-, late- passage and celecoxib-treated hMSCs at a 1∶10 ratio (MSC:MNC). The proliferation of hMNCs was measured by a BrdU assay after 72 hours. n = 3. (**<i>P</i><0.01).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression", "immune-inhibitory", "late-passage", "hmscs", "regulated", "pge2"], "article_id"=>1126511, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Declined_immune_inhibitory_effect_of_late_passage_hMSCs_is_regulated_by_PGE2_and_COX_2_/1126511", "title"=>"Declined immune-inhibitory effect of late-passage hMSCs is regulated by PGE2 and COX-2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-04 02:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1620512"], "description"=>"<p>(A) Phosphorylation of p38 MAPK was investigated by Western blot analysis after treatment with IFN-γ and TNF-α, as indicated. (B, C) Expression of the phosphorylated form of p38 MAPK in early- and late-passage hMSCs was determined by immunocytochemistry after treatment with IFN-γ and TNF-α for 30 minutes. (D, E) After treating cells with SB203580, the expression levels of COX-2 and p-p38 were confirmed by Western blot analysis. Cells were treated with IFN-γ and TNF-α for 30 minutes to detect the expression of p-p38 and for 24 hours to detect COX-2 expression. n = 3. (*<i>P</i><0.05).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression", "kinase", "senescence-associated", "cox-2"], "article_id"=>1126516, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_p38_MAP_kinase_is_responsible_for_senescence_associated_COX_2_expression_/1126516", "title"=>"p38 MAP kinase is responsible for senescence-associated COX-2 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-04 02:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1620513", "https://ndownloader.figshare.com/files/1620514", "https://ndownloader.figshare.com/files/1620515"], "description"=>"<div><p>Because human mesenchymal stem cells (hMSC) have profound immunomodulatory effects, many attempts have been made to use hMSCs in preclinical and clinical trials. For hMSCs to be used in therapy, a large population of hMSCs must be generated by in vitro expansion. However, the immunomodulatory changes following the in vitro expansion of hMSCs have not been elucidated. In this study, we evaluated the effect of replicative senescence on the immunomodulatory ability of hMSCs in vitro and in vivo. Late-passage hMSCs showed impaired suppressive effect on mitogen-induced mononuclear cell proliferation. Strikingly, late-passage hMSCs had a significantly compromised protective effect against mouse experimental colitis, which was confirmed by gross and histologic examination. Among the anti-inflammatory cytokines, the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and the expression of its primary enzyme, cyclooxygenase-2 (COX-2), were profoundly increased by pre-stimulation with interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), and this response was significantly decreased with consecutive passages. We demonstrated that the impaired phosphorylation activity of p38 MAP kinase (p38 MAPK) in late-passage hMSCs led to a compromised immunomodulatory ability through the regulation of COX-2. In conclusion, our data indicate that the immunomodulatory ability of hMSCs gradually declines with consecutive passages via a p38-mediated alteration of COX-2 and PGE<sub>2</sub> levels.</p></div>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "mesenchymal stem cells", "immunology", "Immune response", "Immune suppression", "p38", "mapk-mediated", "alteration", "regulates", "immunomodulatory", "mesenchymal", "aging"], "article_id"=>1126517, "categories"=>["Biological Sciences"], "users"=>["Kyung-Rok Yu", "Jin Young Lee", "Hyung-Sik Kim", "In-Sun Hong", "Soon Won Choi", "Yoojin Seo", "Insung Kang", "Jae-Jun Kim", "Byung-Chul Lee", "Seunghee Lee", "Andreas Kurtz", "Kwang-Won Seo", "Kyung-Sun Kang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102426.s001", "https://dx.doi.org/10.1371/journal.pone.0102426.s002", "https://dx.doi.org/10.1371/journal.pone.0102426.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_p38_MAPK_Mediated_Alteration_of_COX_2_PGE_2_Regulates_Immunomodulatory_Properties_in_Human_Mesenchymal_Stem_Cell_Aging/1126517", "title"=>"A p38 MAPK-Mediated Alteration of COX-2/PGE<sub>2</sub> Regulates Immunomodulatory Properties in Human Mesenchymal Stem Cell Aging", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-08-04 02:43:25"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"24", "full-text"=>"28", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"43", "full-text"=>"29", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"21", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"22", "full-text"=>"20", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"51", "full-text"=>"48", "pdf"=>"28", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"48", "full-text"=>"46", "pdf"=>"33", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"31", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"62", "full-text"=>"50", "pdf"=>"37", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"31", "full-text"=>"21", "pdf"=>"11", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"28", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"26", "full-text"=>"20", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"20", "full-text"=>"16", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"23", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"20", "full-text"=>"25", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[280]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[287]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[286]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[278]}]}
Loading … Spinner
There are currently no alerts