Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages
[Display omitted] •Luteolin inhibits the secretion of HMGB1 and aggravation of inflammatory cascades.•Luteolin destabilizes the protein levels of c-Jun and Akt (Hsp90 client proteins).•Luteolin protects against LPS induced lethality in vivo. Septic diseases represent the prevalent complications in i...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2014-01, Vol.443 (1), p.326-332 |
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| creator | Chen, Dan Bi, Aijing Dong, Xiaoliang Jiang, Yi Rui, Bing Liu, Jinjiao Yin, Zhimin Luo, Lan |
| description | [Display omitted]
•Luteolin inhibits the secretion of HMGB1 and aggravation of inflammatory cascades.•Luteolin destabilizes the protein levels of c-Jun and Akt (Hsp90 client proteins).•Luteolin protects against LPS induced lethality in vivo.
Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases. |
| doi_str_mv | 10.1016/j.bbrc.2013.11.122 |
| format | Article |
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•Luteolin inhibits the secretion of HMGB1 and aggravation of inflammatory cascades.•Luteolin destabilizes the protein levels of c-Jun and Akt (Hsp90 client proteins).•Luteolin protects against LPS induced lethality in vivo.
Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2013.11.122</identifier><identifier>PMID: 24321097</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; c-Jun ; Cell Line ; Disease Models, Animal ; Heat shock protein 90 ; HEK293 Cells ; High mobility group B-1 ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; HSP90 Heat-Shock Proteins - metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases - metabolism ; Lipopolysaccharide ; Lipopolysaccharides ; Luteolin ; Luteolin - pharmacology ; Luteolin - therapeutic use ; Macrophage ; Macrophages - drug effects ; Mice ; Mice, Inbred BALB C ; Proto-Oncogene Proteins c-akt - metabolism ; Sepsis - drug therapy ; Signal Transduction - drug effects</subject><ispartof>Biochemical and biophysical research communications, 2014-01, Vol.443 (1), p.326-332</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-be9863d6e568bb93b957d52dd6089277f51508d54d47266cc9b7c4752ea2a0b93</citedby><cites>FETCH-LOGICAL-c389t-be9863d6e568bb93b957d52dd6089277f51508d54d47266cc9b7c4752ea2a0b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2013.11.122$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24321097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Dan</creatorcontrib><creatorcontrib>Bi, Aijing</creatorcontrib><creatorcontrib>Dong, Xiaoliang</creatorcontrib><creatorcontrib>Jiang, Yi</creatorcontrib><creatorcontrib>Rui, Bing</creatorcontrib><creatorcontrib>Liu, Jinjiao</creatorcontrib><creatorcontrib>Yin, Zhimin</creatorcontrib><creatorcontrib>Luo, Lan</creatorcontrib><title>Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>[Display omitted]
•Luteolin inhibits the secretion of HMGB1 and aggravation of inflammatory cascades.•Luteolin destabilizes the protein levels of c-Jun and Akt (Hsp90 client proteins).•Luteolin protects against LPS induced lethality in vivo.
Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>c-Jun</subject><subject>Cell Line</subject><subject>Disease Models, Animal</subject><subject>Heat shock protein 90</subject><subject>HEK293 Cells</subject><subject>High mobility group B-1</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides</subject><subject>Luteolin</subject><subject>Luteolin - pharmacology</subject><subject>Luteolin - therapeutic use</subject><subject>Macrophage</subject><subject>Macrophages - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Sepsis - drug therapy</subject><subject>Signal Transduction - drug effects</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkb1uFDEUhS0EIkvgBSiQS5oZfD0z9liiQREJkVZKEyQ6yz93Ml7mZ7G9Efv2eLWBEqWxi_udI_t-hLwHVgMD8WlXWxtdzRk0NUANnL8gG2CKVRxY-5JsGGOi4gp-XJA3Ke0YA2iFek0ueNsURMkNmbaHjOsUFoq_x2BDTtQsOVRhGSYzzyav8UhxGNCViT1SO63uZ1geaB6RGpfDY8hHug50RJNpGsuU7uOasTQqRss5GxfX_WgeML0lrwYzJXz3dF-S79df76--Vdu7m9urL9vKNb3KlUXVi8YL7ERvrWqs6qTvuPeC9YpLOXTQsd53rW8lF8I5ZaVrZcfRcMNK4JJ8PPeWl_w6YMp6DsnhNJkF10PSIETPO8X7Z6CtYrKRvBEF5We0_CeliIPexzCbeNTA9EmI3umTEH0SogF0EVJCH576D3ZG_y_y10ABPp8BLAt5DBh1cgEXhz7EsnTt1_C__j85MpxU</recordid><startdate>20140103</startdate><enddate>20140103</enddate><creator>Chen, Dan</creator><creator>Bi, Aijing</creator><creator>Dong, Xiaoliang</creator><creator>Jiang, Yi</creator><creator>Rui, Bing</creator><creator>Liu, Jinjiao</creator><creator>Yin, Zhimin</creator><creator>Luo, Lan</creator><general>Elsevier Inc</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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20140103</creationdate><title>Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages</title><author>Chen, Dan ; Bi, Aijing ; Dong, Xiaoliang ; Jiang, Yi ; Rui, Bing ; Liu, Jinjiao ; Yin, Zhimin ; Luo, Lan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-be9863d6e568bb93b957d52dd6089277f51508d54d47266cc9b7c4752ea2a0b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>c-Jun</topic><topic>Cell Line</topic><topic>Disease Models, Animal</topic><topic>Heat shock protein 90</topic><topic>HEK293 Cells</topic><topic>High mobility group B-1</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharides</topic><topic>Luteolin</topic><topic>Luteolin - pharmacology</topic><topic>Luteolin - therapeutic use</topic><topic>Macrophage</topic><topic>Macrophages - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Sepsis - drug therapy</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Dan</creatorcontrib><creatorcontrib>Bi, Aijing</creatorcontrib><creatorcontrib>Dong, Xiaoliang</creatorcontrib><creatorcontrib>Jiang, Yi</creatorcontrib><creatorcontrib>Rui, Bing</creatorcontrib><creatorcontrib>Liu, Jinjiao</creatorcontrib><creatorcontrib>Yin, Zhimin</creatorcontrib><creatorcontrib>Luo, Lan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Dan</au><au>Bi, Aijing</au><au>Dong, Xiaoliang</au><au>Jiang, Yi</au><au>Rui, Bing</au><au>Liu, Jinjiao</au><au>Yin, Zhimin</au><au>Luo, Lan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2014-01-03</date><risdate>2014</risdate><volume>443</volume><issue>1</issue><spage>326</spage><epage>332</epage><pages>326-332</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>[Display omitted]
•Luteolin inhibits the secretion of HMGB1 and aggravation of inflammatory cascades.•Luteolin destabilizes the protein levels of c-Jun and Akt (Hsp90 client proteins).•Luteolin protects against LPS induced lethality in vivo.
Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24321097</pmid><doi>10.1016/j.bbrc.2013.11.122</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anti-Inflammatory Agents, Non-Steroidal - therapeutic use c-Jun Cell Line Disease Models, Animal Heat shock protein 90 HEK293 Cells High mobility group B-1 HSP90 Heat-Shock Proteins - antagonists & inhibitors HSP90 Heat-Shock Proteins - metabolism Humans JNK Mitogen-Activated Protein Kinases - metabolism Lipopolysaccharide Lipopolysaccharides Luteolin Luteolin - pharmacology Luteolin - therapeutic use Macrophage Macrophages - drug effects Mice Mice, Inbred BALB C Proto-Oncogene Proteins c-akt - metabolism Sepsis - drug therapy Signal Transduction - drug effects |
| title | Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages |
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