Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes
It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like sy...
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| Veröffentlicht in: | International immunopharmacology 2013-02, Vol.15 (2), p.400-405 |
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| creator | Kloesch, Burkhard Becker, Tatjana Dietersdorfer, Elisabeth Kiener, Hans Steiner, Guenter |
| description | It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA).
MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and −7 was checked with specific antibodies.
Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis.
The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.
► Curcumin diminished IL-1β and PMA-induced IL-6 expression in human synovial fibroblasts. ► Curcumin inhibited activation of NF-κB and induced deactivation of ERK1/2. ► High concentrations of curcumin led to a decrease in cell viability and initiate apoptosis. |
| doi_str_mv | 10.1016/j.intimp.2013.01.003 |
| format | Article |
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MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and −7 was checked with specific antibodies.
Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis.
The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.
► Curcumin diminished IL-1β and PMA-induced IL-6 expression in human synovial fibroblasts. ► Curcumin inhibited activation of NF-κB and induced deactivation of ERK1/2. ► High concentrations of curcumin led to a decrease in cell viability and initiate apoptosis.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2013.01.003</identifier><identifier>PMID: 23347846</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - adverse effects ; Apoptosis ; Apoptosis - drug effects ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - immunology ; Cell Line ; Curcumin ; Curcumin - administration & dosage ; Curcumin - adverse effects ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Fibroblasts - drug effects ; Fibroblasts - pathology ; Humans ; IL-6 ; Interleukin-1beta - immunology ; Interleukin-6 - metabolism ; NF-kappa B - metabolism ; Polyphenols - administration & dosage ; Polyphenols - adverse effects ; Synovial fibroblasts ; Synovial Membrane - pathology ; Tetradecanoylphorbol Acetate - analogs & derivatives ; Tetradecanoylphorbol Acetate - immunology ; Vascular Endothelial Growth Factor A - metabolism ; VEGF-A</subject><ispartof>International immunopharmacology, 2013-02, Vol.15 (2), p.400-405</ispartof><rights>2013 Elsevier B.V.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-235646d7b17a04ab6880b15714151282c3fad28bf60d2a6aeb3e54a13cd44c163</citedby><cites>FETCH-LOGICAL-c428t-235646d7b17a04ab6880b15714151282c3fad28bf60d2a6aeb3e54a13cd44c163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2013.01.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23347846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kloesch, Burkhard</creatorcontrib><creatorcontrib>Becker, Tatjana</creatorcontrib><creatorcontrib>Dietersdorfer, Elisabeth</creatorcontrib><creatorcontrib>Kiener, Hans</creatorcontrib><creatorcontrib>Steiner, Guenter</creatorcontrib><title>Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA).
MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and −7 was checked with specific antibodies.
Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis.
The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.
► Curcumin diminished IL-1β and PMA-induced IL-6 expression in human synovial fibroblasts. ► Curcumin inhibited activation of NF-κB and induced deactivation of ERK1/2. ► High concentrations of curcumin led to a decrease in cell viability and initiate apoptosis.</description><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Cell Line</subject><subject>Curcumin</subject><subject>Curcumin - administration & dosage</subject><subject>Curcumin - adverse effects</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - pathology</subject><subject>Humans</subject><subject>IL-6</subject><subject>Interleukin-1beta - immunology</subject><subject>Interleukin-6 - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Polyphenols - administration & dosage</subject><subject>Polyphenols - adverse effects</subject><subject>Synovial fibroblasts</subject><subject>Synovial Membrane - pathology</subject><subject>Tetradecanoylphorbol Acetate - analogs & derivatives</subject><subject>Tetradecanoylphorbol Acetate - immunology</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF-A</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rHSEUhqU0NB_tPyjFZTcz9aijdlMIIUkDgW7StTiOcr2d0ak6gfn3Ndy0y67O4fB-cB6EPgLpgYD4cuxDrGFZe0qA9QR6QtgbdAFKqg4kGd62fRCyG6T4eo4uSzkS0u4c3qFzyhiXiosLdLhuIV2IfjbLYmrKOzZxwmZNa001WOy8d7YWnDyuB4fXNO_rwcU0Y7tluy0h4hTxYVtMxD6MOY2zKbWbwy-Hyx7Tc0h2r668R2fezMV9eJ1X6Ofd7dPN9-7xx_3DzfVjZzlVtaNsEFxMcgRpCDejUIqMMEjgMABV1DJvJqpGL8hEjTBuZG7gBpidOLcg2BX6fMpdc_q9uVL1Eop182yiS1vRwIBLIqgiTcpPUptTKdl5veawmLxrIPqFsT7qE2P9wlgT0I1xs316bdjGxU3_TH-hNsG3k8C1P5-Dy7rY4KJ1U8iNpZ5S-H_DH6N8kPk</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Kloesch, Burkhard</creator><creator>Becker, Tatjana</creator><creator>Dietersdorfer, Elisabeth</creator><creator>Kiener, Hans</creator><creator>Steiner, Guenter</creator><general>Elsevier B.V</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></search><sort><creationdate>201302</creationdate><title>Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes</title><author>Kloesch, Burkhard ; Becker, Tatjana ; Dietersdorfer, Elisabeth ; Kiener, Hans ; Steiner, Guenter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-235646d7b17a04ab6880b15714151282c3fad28bf60d2a6aeb3e54a13cd44c163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Cell Line</topic><topic>Curcumin</topic><topic>Curcumin - administration & dosage</topic><topic>Curcumin - adverse effects</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - pathology</topic><topic>Humans</topic><topic>IL-6</topic><topic>Interleukin-1beta - immunology</topic><topic>Interleukin-6 - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Polyphenols - administration & dosage</topic><topic>Polyphenols - adverse effects</topic><topic>Synovial fibroblasts</topic><topic>Synovial Membrane - pathology</topic><topic>Tetradecanoylphorbol Acetate - analogs & derivatives</topic><topic>Tetradecanoylphorbol Acetate - immunology</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF-A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kloesch, Burkhard</creatorcontrib><creatorcontrib>Becker, Tatjana</creatorcontrib><creatorcontrib>Dietersdorfer, Elisabeth</creatorcontrib><creatorcontrib>Kiener, Hans</creatorcontrib><creatorcontrib>Steiner, Guenter</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><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kloesch, Burkhard</au><au>Becker, Tatjana</au><au>Dietersdorfer, Elisabeth</au><au>Kiener, Hans</au><au>Steiner, Guenter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2013-02</date><risdate>2013</risdate><volume>15</volume><issue>2</issue><spage>400</spage><epage>405</epage><pages>400-405</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA).
MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and −7 was checked with specific antibodies.
Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis.
The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA.
► Curcumin diminished IL-1β and PMA-induced IL-6 expression in human synovial fibroblasts. ► Curcumin inhibited activation of NF-κB and induced deactivation of ERK1/2. ► High concentrations of curcumin led to a decrease in cell viability and initiate apoptosis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23347846</pmid><doi>10.1016/j.intimp.2013.01.003</doi><tpages>6</tpages></addata></record> |
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| subjects | Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - adverse effects Apoptosis Apoptosis - drug effects Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - immunology Cell Line Curcumin Curcumin - administration & dosage Curcumin - adverse effects Extracellular Signal-Regulated MAP Kinases - metabolism Fibroblasts - drug effects Fibroblasts - pathology Humans IL-6 Interleukin-1beta - immunology Interleukin-6 - metabolism NF-kappa B - metabolism Polyphenols - administration & dosage Polyphenols - adverse effects Synovial fibroblasts Synovial Membrane - pathology Tetradecanoylphorbol Acetate - analogs & derivatives Tetradecanoylphorbol Acetate - immunology Vascular Endothelial Growth Factor A - metabolism VEGF-A |
| title | Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes |
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