Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase
Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils. This study investigated tissue factor production by peripheral monocytes after stimulation wi...
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description | Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils.
This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase.
Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors.
Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKCμ) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor.
Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved. |
doi_str_mv | 10.1016/j.bcmd.2014.10.005 |
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This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase.
Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors.
Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKCμ) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor.
Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved.</description><identifier>ISSN: 1079-9796</identifier><identifier>EISSN: 1096-0961</identifier><identifier>DOI: 10.1016/j.bcmd.2014.10.005</identifier><identifier>PMID: 25465717</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Calcium Channel Blockers - pharmacology ; Carbazoles - pharmacology ; Disseminated intravascular coagulation ; Enzyme Inhibitors - pharmacology ; Estrenes - pharmacology ; Flavonoids - pharmacology ; Gallic Acid - analogs & derivatives ; Gallic Acid - pharmacology ; Gene Expression Regulation ; Humans ; Imidazoles - pharmacology ; Indoles - pharmacology ; Leukocyte Elastase - pharmacology ; Maleimides - pharmacology ; Monocyte ; Monocytes - cytology ; Monocytes - drug effects ; Monocytes - metabolism ; Neutrophil elastase ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; Primary Cell Culture ; Protein kinase C ; Protein Kinase C - genetics ; Protein Kinase C - metabolism ; Protein Kinase Inhibitors - pharmacology ; Pyridines - pharmacology ; Pyrrolidinones - pharmacology ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction ; Thromboplastin - genetics ; Thromboplastin - metabolism ; Tissue factor ; Type C Phospholipases - genetics ; Type C Phospholipases - metabolism</subject><ispartof>Blood cells, molecules, & diseases, 2015-02, Vol.54 (2), p.206-209</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-ced7e197c26c5a623dadbb4d3551bf65d2739cb89119b06a9503b0d5a46f14943</citedby><cites>FETCH-LOGICAL-c356t-ced7e197c26c5a623dadbb4d3551bf65d2739cb89119b06a9503b0d5a46f14943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bcmd.2014.10.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25465717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawata, Jin</creatorcontrib><creatorcontrib>Aoki, Manabu</creatorcontrib><creatorcontrib>Ishimaru, Yasuji</creatorcontrib><creatorcontrib>Ono, Tomomichi</creatorcontrib><creatorcontrib>Sagara, Katsurou</creatorcontrib><creatorcontrib>Narahara, Shinji</creatorcontrib><creatorcontrib>Matsmoto, Tamami</creatorcontrib><creatorcontrib>Hirose, Eiji</creatorcontrib><creatorcontrib>Yamaguchi, Yasuo</creatorcontrib><title>Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase</title><title>Blood cells, molecules, & diseases</title><addtitle>Blood Cells Mol Dis</addtitle><description>Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils.
This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase.
Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors.
Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKCμ) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor.
Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved.</description><subject>Calcium Channel Blockers - pharmacology</subject><subject>Carbazoles - pharmacology</subject><subject>Disseminated intravascular coagulation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Estrenes - pharmacology</subject><subject>Flavonoids - pharmacology</subject><subject>Gallic Acid - analogs & derivatives</subject><subject>Gallic Acid - pharmacology</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Imidazoles - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Leukocyte Elastase - pharmacology</subject><subject>Maleimides - pharmacology</subject><subject>Monocyte</subject><subject>Monocytes - cytology</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>Neutrophil elastase</subject><subject>p38 Mitogen-Activated Protein Kinases - genetics</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Primary Cell Culture</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - genetics</subject><subject>Protein Kinase C - metabolism</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Pyrrolidinones - pharmacology</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Thromboplastin - genetics</subject><subject>Thromboplastin - metabolism</subject><subject>Tissue factor</subject><subject>Type C Phospholipases - genetics</subject><subject>Type C Phospholipases - metabolism</subject><issn>1079-9796</issn><issn>1096-0961</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMofqz-AQ-So5euSdukBryI-AUrXtRryMeUzdI2a5Iq--9N2dWjh2GG4Z2Xdx6EzimZU0L51WquTW_nJaF1XswJYXvomBLBi1x0f5obUYhG8CN0EuOKEEKpuD5ERyWrOWtoc4w-XsAs1eBij32Lk4txBNwqk3zA6-DtaJLzA9Yb3PvBm02CiGNy_dipBBZ_u7TEA4wp-PXSdRg6FZOKcIoOWtVFONv1GXp_uH-7eyoWr4_Pd7eLwlSMp8KAbYCKxpTcMMXLyiqrdW0rxqhuObNlUwmjr0XOrQlXgpFKE8tUzVtai7qaocutb876OUJMsnfRQNepAfwYJeWsrKngtcjScis1wccYoJXr4HoVNpISOfGUKznxlBPPaZd55qOLnf-oe7B_J78As-BmK4D85ZeDIKNxMOTHXACTpPXuP_8frriH4A</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Kawata, Jin</creator><creator>Aoki, Manabu</creator><creator>Ishimaru, Yasuji</creator><creator>Ono, Tomomichi</creator><creator>Sagara, Katsurou</creator><creator>Narahara, Shinji</creator><creator>Matsmoto, Tamami</creator><creator>Hirose, Eiji</creator><creator>Yamaguchi, Yasuo</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></search><sort><creationdate>20150201</creationdate><title>Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase</title><author>Kawata, Jin ; Aoki, Manabu ; Ishimaru, Yasuji ; Ono, Tomomichi ; Sagara, Katsurou ; Narahara, Shinji ; Matsmoto, Tamami ; Hirose, Eiji ; Yamaguchi, Yasuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ced7e197c26c5a623dadbb4d3551bf65d2739cb89119b06a9503b0d5a46f14943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Calcium Channel Blockers - pharmacology</topic><topic>Carbazoles - pharmacology</topic><topic>Disseminated intravascular coagulation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Estrenes - pharmacology</topic><topic>Flavonoids - pharmacology</topic><topic>Gallic Acid - analogs & derivatives</topic><topic>Gallic Acid - pharmacology</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Imidazoles - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Leukocyte Elastase - pharmacology</topic><topic>Maleimides - pharmacology</topic><topic>Monocyte</topic><topic>Monocytes - cytology</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Neutrophil elastase</topic><topic>p38 Mitogen-Activated Protein Kinases - genetics</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Primary Cell Culture</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - genetics</topic><topic>Protein Kinase C - metabolism</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Pyrrolidinones - pharmacology</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Thromboplastin - genetics</topic><topic>Thromboplastin - metabolism</topic><topic>Tissue factor</topic><topic>Type C Phospholipases - genetics</topic><topic>Type C Phospholipases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawata, Jin</creatorcontrib><creatorcontrib>Aoki, Manabu</creatorcontrib><creatorcontrib>Ishimaru, Yasuji</creatorcontrib><creatorcontrib>Ono, Tomomichi</creatorcontrib><creatorcontrib>Sagara, Katsurou</creatorcontrib><creatorcontrib>Narahara, Shinji</creatorcontrib><creatorcontrib>Matsmoto, Tamami</creatorcontrib><creatorcontrib>Hirose, Eiji</creatorcontrib><creatorcontrib>Yamaguchi, Yasuo</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>Blood cells, molecules, & diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawata, Jin</au><au>Aoki, Manabu</au><au>Ishimaru, Yasuji</au><au>Ono, Tomomichi</au><au>Sagara, Katsurou</au><au>Narahara, Shinji</au><au>Matsmoto, Tamami</au><au>Hirose, Eiji</au><au>Yamaguchi, Yasuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase</atitle><jtitle>Blood cells, molecules, & diseases</jtitle><addtitle>Blood Cells Mol Dis</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>54</volume><issue>2</issue><spage>206</spage><epage>209</epage><pages>206-209</pages><issn>1079-9796</issn><eissn>1096-0961</eissn><abstract>Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils.
This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase.
Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors.
Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKCμ) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor.
Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25465717</pmid><doi>10.1016/j.bcmd.2014.10.005</doi><tpages>4</tpages></addata></record> |
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subjects | Calcium Channel Blockers - pharmacology Carbazoles - pharmacology Disseminated intravascular coagulation Enzyme Inhibitors - pharmacology Estrenes - pharmacology Flavonoids - pharmacology Gallic Acid - analogs & derivatives Gallic Acid - pharmacology Gene Expression Regulation Humans Imidazoles - pharmacology Indoles - pharmacology Leukocyte Elastase - pharmacology Maleimides - pharmacology Monocyte Monocytes - cytology Monocytes - drug effects Monocytes - metabolism Neutrophil elastase p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism Primary Cell Culture Protein kinase C Protein Kinase C - genetics Protein Kinase C - metabolism Protein Kinase Inhibitors - pharmacology Pyridines - pharmacology Pyrrolidinones - pharmacology RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction Thromboplastin - genetics Thromboplastin - metabolism Tissue factor Type C Phospholipases - genetics Type C Phospholipases - metabolism |
title | Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase |
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