Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines
It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has bee...
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| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e81747 |
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| creator | Gong, Peipei Xu, Xide Shi, Jinlong Ni, Lanchun Huang, Qingfeng Xia, Liang Nie, Dekang Lu, Xiaojian Chen, Jian Shi, Wei |
| description | It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to be involved in the pathology of inflammatory gene expression. In this study, the roles of MSK1 activation in neuroinflammation were investigated.
The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).
Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.
Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation. |
| doi_str_mv | 10.1371/journal.pone.0081747 |
| format | Article |
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The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).
Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.
Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081747</identifier><identifier>PMID: 24349124</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Apoptosis ; Astrocytes ; Astrocytes - metabolism ; Astrocytes - pathology ; Bacteria ; Brain ; Brain injuries ; Brain Injuries - chemically induced ; Brain Injuries - genetics ; Brain Injuries - metabolism ; Brain Injuries - pathology ; Brain injury ; Central nervous system ; Cerebral cortex ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Cytokines ; Disease ; Enzyme-linked immunosorbent assay ; Enzymes ; Gene expression ; Gene Expression Regulation ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - genetics ; Glial Fibrillary Acidic Protein - metabolism ; Head injuries ; Hospitals ; Immunofluorescence ; Inflammation ; Inflammation - chemically induced ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - pathology ; Injections, Intraventricular ; Interleukin 6 ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; Intermediate filament proteins ; Kinases ; Laboratories ; Lipopolysaccharides ; Male ; MAP kinase ; Medical research ; Mitogens ; Mutation ; Nervous system ; Neurodegeneration ; Neurosurgery ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Nitric-oxide synthase ; Phosphorylation ; Primary Cell Culture ; Protein kinases ; Proteins ; Rats ; Rats, Sprague-Dawley ; Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors ; Ribosomal Protein S6 Kinases, 90-kDa - genetics ; Ribosomal Protein S6 Kinases, 90-kDa - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; Signaling ; siRNA ; Synthesis ; Traumatic brain injury ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Ventricle (lateral)</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e81747</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Gong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Gong et al 2013 Gong et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-66c2b4f686c41cfadb3995a441b30fb42d3064a8547e0c6720786642b77c06f73</citedby><cites>FETCH-LOGICAL-c758t-66c2b4f686c41cfadb3995a441b30fb42d3064a8547e0c6720786642b77c06f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859508/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859508/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24349124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mongin, Alexander A.</contributor><creatorcontrib>Gong, Peipei</creatorcontrib><creatorcontrib>Xu, Xide</creatorcontrib><creatorcontrib>Shi, Jinlong</creatorcontrib><creatorcontrib>Ni, Lanchun</creatorcontrib><creatorcontrib>Huang, Qingfeng</creatorcontrib><creatorcontrib>Xia, Liang</creatorcontrib><creatorcontrib>Nie, Dekang</creatorcontrib><creatorcontrib>Lu, Xiaojian</creatorcontrib><creatorcontrib>Chen, Jian</creatorcontrib><creatorcontrib>Shi, Wei</creatorcontrib><title>Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to be involved in the pathology of inflammatory gene expression. In this study, the roles of MSK1 activation in neuroinflammation were investigated.
The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).
Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.
Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation.</description><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Astrocytes</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Bacteria</subject><subject>Brain</subject><subject>Brain injuries</subject><subject>Brain Injuries - chemically induced</subject><subject>Brain Injuries - genetics</subject><subject>Brain Injuries - metabolism</subject><subject>Brain Injuries - pathology</subject><subject>Brain injury</subject><subject>Central nervous system</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Glial fibrillary acidic protein</subject><subject>Glial Fibrillary Acidic Protein - genetics</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Head injuries</subject><subject>Hospitals</subject><subject>Immunofluorescence</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - genetics</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Injections, Intraventricular</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - metabolism</subject><subject>Intermediate filament proteins</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medical research</subject><subject>Mitogens</subject><subject>Mutation</subject><subject>Nervous system</subject><subject>Neurodegeneration</subject><subject>Neurosurgery</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Phosphorylation</subject><subject>Primary Cell Culture</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - genetics</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Synthesis</subject><subject>Traumatic brain injury</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Ventricle (lateral)</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk2uL1DAUhoso7rr6D0QLguCHjkmTJq0fhGXxMrCw4u1rSNO0zdg2NUkX59_4Uz2z0xmmoCCFNJfnvOfwck4UPcVohQnHrzd2coPsVqMd9AqhHHPK70XnuCBpwlJE7p_sz6JH3m8QykjO2MPoLKWEFjil59HvT631Y2vdtpPB2CG2ddybYBs9JLEcqtgHp71PpArmVgZdxaOzQZsh_mEG6XWCY9hLoKzaBqPgVHey7-_E3sQyHq33pux07CwswJqhNaUJZmh2UtWkDmmPkVBMDGIWMmj_OHpQy87rJ_P_Ivr2_t3Xq4_J9c2H9dXldaJ4loeEMZWWtGY5UxSrWlYlKYpMUopLguqSphVBjMo8o1wjxXiKOFhB05JzhVjNyUX0fK87dtaL2VwvMAWWU0pSINZ7orJyI0Zneum2wkoj7i6sa4R0YEGnhVKaaiy1zPOCoqwqEVZMMZxpkhaFRqD1ds42lb2ulB6Ck91CdPkymFY09laQPCsylIPAi1nA2Z-T9uEfJc9UI6EqMNiCmOqNV-KS8pwQlKUMqNVfKPgq3RsF7VUbuF8EvFoEABP0r9DIyXux_vL5_9mb70v25QnbatmF1ttu2nWIX4J0DyoH7eV0fXQOI7GbjoMbYjcdYp4OCHt26vox6DAO5A_j2g3m</recordid><startdate>20131211</startdate><enddate>20131211</enddate><creator>Gong, Peipei</creator><creator>Xu, Xide</creator><creator>Shi, Jinlong</creator><creator>Ni, Lanchun</creator><creator>Huang, Qingfeng</creator><creator>Xia, Liang</creator><creator>Nie, Dekang</creator><creator>Lu, Xiaojian</creator><creator>Chen, Jian</creator><creator>Shi, Wei</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131211</creationdate><title>Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines</title><author>Gong, Peipei ; Xu, Xide ; Shi, Jinlong ; Ni, Lanchun ; Huang, Qingfeng ; Xia, Liang ; Nie, Dekang ; Lu, Xiaojian ; Chen, Jian ; Shi, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-66c2b4f686c41cfadb3995a441b30fb42d3064a8547e0c6720786642b77c06f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Astrocytes</topic><topic>Astrocytes - 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genetics</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Injections, Intraventricular</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - genetics</topic><topic>Interleukin-6 - metabolism</topic><topic>Intermediate filament proteins</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Medical research</topic><topic>Mitogens</topic><topic>Mutation</topic><topic>Nervous system</topic><topic>Neurodegeneration</topic><topic>Neurosurgery</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Phosphorylation</topic><topic>Primary Cell Culture</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - genetics</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Synthesis</topic><topic>Traumatic brain injury</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Ventricle (lateral)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gong, Peipei</creatorcontrib><creatorcontrib>Xu, Xide</creatorcontrib><creatorcontrib>Shi, Jinlong</creatorcontrib><creatorcontrib>Ni, Lanchun</creatorcontrib><creatorcontrib>Huang, Qingfeng</creatorcontrib><creatorcontrib>Xia, Liang</creatorcontrib><creatorcontrib>Nie, Dekang</creatorcontrib><creatorcontrib>Lu, Xiaojian</creatorcontrib><creatorcontrib>Chen, Jian</creatorcontrib><creatorcontrib>Shi, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gong, Peipei</au><au>Xu, Xide</au><au>Shi, Jinlong</au><au>Ni, Lanchun</au><au>Huang, Qingfeng</au><au>Xia, Liang</au><au>Nie, Dekang</au><au>Lu, Xiaojian</au><au>Chen, Jian</au><au>Shi, Wei</au><au>Mongin, Alexander A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-11</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e81747</spage><pages>e81747-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to be involved in the pathology of inflammatory gene expression. In this study, the roles of MSK1 activation in neuroinflammation were investigated.
The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).
Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.
Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24349124</pmid><doi>10.1371/journal.pone.0081747</doi><tpages>e81747</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-12, Vol.8 (12), p.e81747 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1467274432 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animals Apoptosis Astrocytes Astrocytes - metabolism Astrocytes - pathology Bacteria Brain Brain injuries Brain Injuries - chemically induced Brain Injuries - genetics Brain Injuries - metabolism Brain Injuries - pathology Brain injury Central nervous system Cerebral cortex Cerebral Cortex - metabolism Cerebral Cortex - pathology Cytokines Disease Enzyme-linked immunosorbent assay Enzymes Gene expression Gene Expression Regulation Glial fibrillary acidic protein Glial Fibrillary Acidic Protein - genetics Glial Fibrillary Acidic Protein - metabolism Head injuries Hospitals Immunofluorescence Inflammation Inflammation - chemically induced Inflammation - genetics Inflammation - metabolism Inflammation - pathology Injections, Intraventricular Interleukin 6 Interleukin-6 - genetics Interleukin-6 - metabolism Intermediate filament proteins Kinases Laboratories Lipopolysaccharides Male MAP kinase Medical research Mitogens Mutation Nervous system Neurodegeneration Neurosurgery Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Phosphorylation Primary Cell Culture Protein kinases Proteins Rats Rats, Sprague-Dawley Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors Ribosomal Protein S6 Kinases, 90-kDa - genetics Ribosomal Protein S6 Kinases, 90-kDa - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Rodents Signal Transduction Signaling siRNA Synthesis Traumatic brain injury Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Ventricle (lateral) |
| title | Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines |
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