Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway
This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE 2 ). We demonstrated that 0.01 to 10 nM PGE 2 protected dopaminergic neurons against LPS-induced neurotoxicity through a redu...
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| Veröffentlicht in: | Molecular neurobiology 2018-10, Vol.55 (10), p.8001-8013 |
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| creator | Chen, Shih-Heng Sung, Yueh-Feng Oyarzabal, Esteban A. Tan, Yu-Mei Leonard, Jeremy Guo, Mingri Li, Shuo Wang, Qingshan Chu, Chun-Hsien Chen, Shiou-Lan Lu, Ru-Band Hong, Jau-Shyong |
| description | This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE
2
). We demonstrated that 0.01 to 10 nM PGE
2
protected dopaminergic neurons against LPS-induced neurotoxicity through a reduction of microglial release of pro-inflammatory factors in a dose-dependent manner. Mechanistically, neuroprotective effects elicited by PGE
2
were mediated by the inhibition of microglial NOX2, a major superoxide-producing enzyme. This conclusion was supported by (1) the close relationship between inhibition of superoxide and PGE
2
-induced neuroprotective effects; (2) the mediation of PGE
2
-induced reduction of superoxide and neuroprotection via direct inhibition of the catalytic subunit of NOX2, gp91
phox
, rather than through the inhibition of conventional prostaglandin E2 receptors; and (3) abolishment of the neuroprotective effect of PGE
2
in NOX2-deficient cultures. In summary, this study revealed a potential physiological role of PGE
2
in maintaining brain immune homeostasis and protecting neurons via an EP receptor-independent mechanism. |
| doi_str_mv | 10.1007/s12035-018-0965-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6119547</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2009303794</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4284-6239967c12fe0f598dc730a9176e1c8d09d82b1859f0e2847b75ed2dbc52e4813</originalsourceid><addsrcrecordid>eNp1kctu1DAUhi0EokPLA7CzxDpgOxfbG6RqNIVKhVaiXVuOL4mrjD3YTmlehafFoxQQi67O4vz_dy4_AO8w-oARoh8TJqhuK4RZhXjXVs0LsMFtyyuMGXkJNojxuqJdw07Am5TuESIEI_oanBDecMIavgG_bsYluTCFwSk5wW3wyvgcZXbBw2DhTQwpy2GSXjsPdwTuHk3MCZ777Crn7ST3e5lDXODOWqNKp1_gpR9d77LzA_zqVAzD5Aq7oPSs_oC_zwcTw6PTBt6OMczDCCX8Fh5MEco8_pTLGXhl5ZTM26d6Cu4udrfbL9XV9efL7flVpZpyQ9WRmvOOKkysQbblTCtaI8kx7QxWTCOuGekxa7lFphhoT1ujie5VS0zDcH0KPq3cw9zvjV7vn8Qhur2MiwjSif873o1iCA-iw5i3DS2A90-AGH7MJmVxH-boy86CIMRrVFPeFBVeVeUhKUVj_07ASBzjFGucosQpjnGKo4esnlS0fjDxH_l5028oqKSj</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2009303794</pqid></control><display><type>article</type><title>Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway</title><source>SpringerLink Journals - AutoHoldings</source><creator>Chen, Shih-Heng ; Sung, Yueh-Feng ; Oyarzabal, Esteban A. ; Tan, Yu-Mei ; Leonard, Jeremy ; Guo, Mingri ; Li, Shuo ; Wang, Qingshan ; Chu, Chun-Hsien ; Chen, Shiou-Lan ; Lu, Ru-Band ; Hong, Jau-Shyong</creator><creatorcontrib>Chen, Shih-Heng ; Sung, Yueh-Feng ; Oyarzabal, Esteban A. ; Tan, Yu-Mei ; Leonard, Jeremy ; Guo, Mingri ; Li, Shuo ; Wang, Qingshan ; Chu, Chun-Hsien ; Chen, Shiou-Lan ; Lu, Ru-Band ; Hong, Jau-Shyong</creatorcontrib><description>This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE
2
). We demonstrated that 0.01 to 10 nM PGE
2
protected dopaminergic neurons against LPS-induced neurotoxicity through a reduction of microglial release of pro-inflammatory factors in a dose-dependent manner. Mechanistically, neuroprotective effects elicited by PGE
2
were mediated by the inhibition of microglial NOX2, a major superoxide-producing enzyme. This conclusion was supported by (1) the close relationship between inhibition of superoxide and PGE
2
-induced neuroprotective effects; (2) the mediation of PGE
2
-induced reduction of superoxide and neuroprotection via direct inhibition of the catalytic subunit of NOX2, gp91
phox
, rather than through the inhibition of conventional prostaglandin E2 receptors; and (3) abolishment of the neuroprotective effect of PGE
2
in NOX2-deficient cultures. In summary, this study revealed a potential physiological role of PGE
2
in maintaining brain immune homeostasis and protecting neurons via an EP receptor-independent mechanism.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-018-0965-4</identifier><identifier>PMID: 29492849</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Anti-inflammatory agents ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Cell Biology ; CYBB protein ; Dopamine receptors ; Homeostasis ; Inflammation ; Inhibition ; Lipopolysaccharides ; Neurobiology ; Neurology ; Neuronal-glial interactions ; Neuroprotection ; Neurosciences ; Neurotoxicity ; Original Paper ; Physiology ; Prostaglandin E2 ; Prostaglandin E2 receptors ; Rodents ; Superoxide</subject><ispartof>Molecular neurobiology, 2018-10, Vol.55 (10), p.8001-8013</ispartof><rights>This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018</rights><rights>Molecular Neurobiology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4284-6239967c12fe0f598dc730a9176e1c8d09d82b1859f0e2847b75ed2dbc52e4813</citedby><cites>FETCH-LOGICAL-c4284-6239967c12fe0f598dc730a9176e1c8d09d82b1859f0e2847b75ed2dbc52e4813</cites><orcidid>0000-0002-5853-6903</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-018-0965-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-018-0965-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids></links><search><creatorcontrib>Chen, Shih-Heng</creatorcontrib><creatorcontrib>Sung, Yueh-Feng</creatorcontrib><creatorcontrib>Oyarzabal, Esteban A.</creatorcontrib><creatorcontrib>Tan, Yu-Mei</creatorcontrib><creatorcontrib>Leonard, Jeremy</creatorcontrib><creatorcontrib>Guo, Mingri</creatorcontrib><creatorcontrib>Li, Shuo</creatorcontrib><creatorcontrib>Wang, Qingshan</creatorcontrib><creatorcontrib>Chu, Chun-Hsien</creatorcontrib><creatorcontrib>Chen, Shiou-Lan</creatorcontrib><creatorcontrib>Lu, Ru-Band</creatorcontrib><creatorcontrib>Hong, Jau-Shyong</creatorcontrib><title>Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><description>This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE
2
). We demonstrated that 0.01 to 10 nM PGE
2
protected dopaminergic neurons against LPS-induced neurotoxicity through a reduction of microglial release of pro-inflammatory factors in a dose-dependent manner. Mechanistically, neuroprotective effects elicited by PGE
2
were mediated by the inhibition of microglial NOX2, a major superoxide-producing enzyme. This conclusion was supported by (1) the close relationship between inhibition of superoxide and PGE
2
-induced neuroprotective effects; (2) the mediation of PGE
2
-induced reduction of superoxide and neuroprotection via direct inhibition of the catalytic subunit of NOX2, gp91
phox
, rather than through the inhibition of conventional prostaglandin E2 receptors; and (3) abolishment of the neuroprotective effect of PGE
2
in NOX2-deficient cultures. In summary, this study revealed a potential physiological role of PGE
2
in maintaining brain immune homeostasis and protecting neurons via an EP receptor-independent mechanism.</description><subject>Anti-inflammatory agents</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Cell Biology</subject><subject>CYBB protein</subject><subject>Dopamine receptors</subject><subject>Homeostasis</subject><subject>Inflammation</subject><subject>Inhibition</subject><subject>Lipopolysaccharides</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuronal-glial interactions</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Neurotoxicity</subject><subject>Original Paper</subject><subject>Physiology</subject><subject>Prostaglandin E2</subject><subject>Prostaglandin E2 receptors</subject><subject>Rodents</subject><subject>Superoxide</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kctu1DAUhi0EokPLA7CzxDpgOxfbG6RqNIVKhVaiXVuOL4mrjD3YTmlehafFoxQQi67O4vz_dy4_AO8w-oARoh8TJqhuK4RZhXjXVs0LsMFtyyuMGXkJNojxuqJdw07Am5TuESIEI_oanBDecMIavgG_bsYluTCFwSk5wW3wyvgcZXbBw2DhTQwpy2GSXjsPdwTuHk3MCZ777Crn7ST3e5lDXODOWqNKp1_gpR9d77LzA_zqVAzD5Aq7oPSs_oC_zwcTw6PTBt6OMczDCCX8Fh5MEco8_pTLGXhl5ZTM26d6Cu4udrfbL9XV9efL7flVpZpyQ9WRmvOOKkysQbblTCtaI8kx7QxWTCOuGekxa7lFphhoT1ujie5VS0zDcH0KPq3cw9zvjV7vn8Qhur2MiwjSif873o1iCA-iw5i3DS2A90-AGH7MJmVxH-boy86CIMRrVFPeFBVeVeUhKUVj_07ASBzjFGucosQpjnGKo4esnlS0fjDxH_l5028oqKSj</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Chen, Shih-Heng</creator><creator>Sung, Yueh-Feng</creator><creator>Oyarzabal, Esteban A.</creator><creator>Tan, Yu-Mei</creator><creator>Leonard, Jeremy</creator><creator>Guo, Mingri</creator><creator>Li, Shuo</creator><creator>Wang, Qingshan</creator><creator>Chu, Chun-Hsien</creator><creator>Chen, Shiou-Lan</creator><creator>Lu, Ru-Band</creator><creator>Hong, Jau-Shyong</creator><general>Springer US</general><general>Springer Nature 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Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway</title><author>Chen, Shih-Heng ; Sung, Yueh-Feng ; Oyarzabal, Esteban A. ; Tan, Yu-Mei ; Leonard, Jeremy ; Guo, Mingri ; Li, Shuo ; Wang, Qingshan ; Chu, Chun-Hsien ; Chen, Shiou-Lan ; Lu, Ru-Band ; Hong, Jau-Shyong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4284-6239967c12fe0f598dc730a9176e1c8d09d82b1859f0e2847b75ed2dbc52e4813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anti-inflammatory agents</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Cell Biology</topic><topic>CYBB protein</topic><topic>Dopamine receptors</topic><topic>Homeostasis</topic><topic>Inflammation</topic><topic>Inhibition</topic><topic>Lipopolysaccharides</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuronal-glial interactions</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Neurotoxicity</topic><topic>Original Paper</topic><topic>Physiology</topic><topic>Prostaglandin E2</topic><topic>Prostaglandin E2 receptors</topic><topic>Rodents</topic><topic>Superoxide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Shih-Heng</creatorcontrib><creatorcontrib>Sung, Yueh-Feng</creatorcontrib><creatorcontrib>Oyarzabal, Esteban A.</creatorcontrib><creatorcontrib>Tan, Yu-Mei</creatorcontrib><creatorcontrib>Leonard, Jeremy</creatorcontrib><creatorcontrib>Guo, Mingri</creatorcontrib><creatorcontrib>Li, Shuo</creatorcontrib><creatorcontrib>Wang, Qingshan</creatorcontrib><creatorcontrib>Chu, Chun-Hsien</creatorcontrib><creatorcontrib>Chen, 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Ru-Band</au><au>Hong, Jau-Shyong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><date>2018-10-01</date><risdate>2018</risdate><volume>55</volume><issue>10</issue><spage>8001</spage><epage>8013</epage><pages>8001-8013</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE
2
). We demonstrated that 0.01 to 10 nM PGE
2
protected dopaminergic neurons against LPS-induced neurotoxicity through a reduction of microglial release of pro-inflammatory factors in a dose-dependent manner. Mechanistically, neuroprotective effects elicited by PGE
2
were mediated by the inhibition of microglial NOX2, a major superoxide-producing enzyme. This conclusion was supported by (1) the close relationship between inhibition of superoxide and PGE
2
-induced neuroprotective effects; (2) the mediation of PGE
2
-induced reduction of superoxide and neuroprotection via direct inhibition of the catalytic subunit of NOX2, gp91
phox
, rather than through the inhibition of conventional prostaglandin E2 receptors; and (3) abolishment of the neuroprotective effect of PGE
2
in NOX2-deficient cultures. In summary, this study revealed a potential physiological role of PGE
2
in maintaining brain immune homeostasis and protecting neurons via an EP receptor-independent mechanism.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29492849</pmid><doi>10.1007/s12035-018-0965-4</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-5853-6903</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| issn | 0893-7648 1559-1182 |
| language | eng |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Anti-inflammatory agents Biomedical and Life Sciences Biomedicine Brain Cell Biology CYBB protein Dopamine receptors Homeostasis Inflammation Inhibition Lipopolysaccharides Neurobiology Neurology Neuronal-glial interactions Neuroprotection Neurosciences Neurotoxicity Original Paper Physiology Prostaglandin E2 Prostaglandin E2 receptors Rodents Superoxide |
| title | Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway |
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