LL37 induces VEGF expression in dental pulp cells through ERK signalling
Aim To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved. Methodology Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was...
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| Veröffentlicht in: | International endodontic journal 2015-07, Vol.48 (7), p.673-679 |
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| container_title | International endodontic journal |
| container_volume | 48 |
| creator | Khung, R. Shiba, H. Kajiya, M. Kittaka, M. Ouhara, K. Takeda, K. Mizuno, N. Fujita, T. Komatsuzawa, H. Kurihara, H. |
| description | Aim
To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.
Methodology
Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was performed with MAPK or NF‐κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real‐time PCR, ELISA and Western blot, respectively. Data were analysed using t‐tests.
Results
LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P |
| doi_str_mv | 10.1111/iej.12365 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmed_primary_25100161</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>IEJ12365</sourcerecordid><originalsourceid>FETCH-LOGICAL-i3225-ee1ebc046a5a4c55477896cdd8bebe7938e33422be595d1e6026317fa448f8d33</originalsourceid><addsrcrecordid>eNo9kMtOwzAQRS0EoqWw4AeQfyCtH7GdLFGVvohA4r2znGTaurhpFDei_XtCC53NHc3cM9JchG4p6dO2BhZWfcq4FGeoS1sJmIjpOeoSGvKARZHooCvvV4QQQTi9RB0mKCFU0i6apClX2JZFk4PH78l4hGFX1eC93ZTtHBdQbo3DVeMqnINzHm-X9aZZLHHy_IC9XZTGOVsurtHF3DgPN3_aQ2-j5HU4CdKn8XR4nwaWMyYCAApZTkJphAlzIUKloljmRRFlkIGKeQSch4xlIGJRUJCESU7V3IRhNI8Kznvo7ni3arI1FLqq7drUe_3_UmsYHA3f1sH-tKdE_2al26z0ISs9TWaHpiWCI2H9FnYnwtRfWiquhP54HGs6e-Hqk890zH8AlM5o_Q</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>LL37 induces VEGF expression in dental pulp cells through ERK signalling</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Khung, R. ; Shiba, H. ; Kajiya, M. ; Kittaka, M. ; Ouhara, K. ; Takeda, K. ; Mizuno, N. ; Fujita, T. ; Komatsuzawa, H. ; Kurihara, H.</creator><creatorcontrib>Khung, R. ; Shiba, H. ; Kajiya, M. ; Kittaka, M. ; Ouhara, K. ; Takeda, K. ; Mizuno, N. ; Fujita, T. ; Komatsuzawa, H. ; Kurihara, H.</creatorcontrib><description>Aim
To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.
Methodology
Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was performed with MAPK or NF‐κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real‐time PCR, ELISA and Western blot, respectively. Data were analysed using t‐tests.
Results
LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre‐treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37‐induced ERK1/2 phosphorylation.
Conclusions
LL37 activated the ERK pathway to boost VEGF secretion from human pulp cells. Because of this angiogenic effect and its reported induction of pulp cell migration and antimicrobial activity against cariogenic bacteria, LL37 may be applicable as a pulp capping material.</description><identifier>ISSN: 0143-2885</identifier><identifier>EISSN: 1365-2591</identifier><identifier>DOI: 10.1111/iej.12365</identifier><identifier>PMID: 25100161</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Anti-Bacterial Agents - pharmacology ; Antimicrobial Cationic Peptides ; Bicuspid ; Blotting, Western ; Cathelicidins - pharmacology ; Cell Culture Techniques ; Cell Movement - drug effects ; Cells, Cultured ; Dental Pulp - cytology ; Dental Pulp - drug effects ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; ERK ; Humans ; In Vitro Techniques ; LL37 ; MAP Kinase Signaling System - drug effects ; Neovascularization, Physiologic - drug effects ; Phosphorylation ; pulp cells ; Real-Time Polymerase Chain Reaction ; Signal Transduction - drug effects ; Up-Regulation ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - drug effects</subject><ispartof>International endodontic journal, 2015-07, Vol.48 (7), p.673-679</ispartof><rights>2014 International Endodontic Journal. Published by John Wiley & Sons Ltd</rights><rights>2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fiej.12365$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fiej.12365$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25100161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khung, R.</creatorcontrib><creatorcontrib>Shiba, H.</creatorcontrib><creatorcontrib>Kajiya, M.</creatorcontrib><creatorcontrib>Kittaka, M.</creatorcontrib><creatorcontrib>Ouhara, K.</creatorcontrib><creatorcontrib>Takeda, K.</creatorcontrib><creatorcontrib>Mizuno, N.</creatorcontrib><creatorcontrib>Fujita, T.</creatorcontrib><creatorcontrib>Komatsuzawa, H.</creatorcontrib><creatorcontrib>Kurihara, H.</creatorcontrib><title>LL37 induces VEGF expression in dental pulp cells through ERK signalling</title><title>International endodontic journal</title><addtitle>Int Endod J</addtitle><description>Aim
To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.
Methodology
Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was performed with MAPK or NF‐κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real‐time PCR, ELISA and Western blot, respectively. Data were analysed using t‐tests.
Results
LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre‐treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37‐induced ERK1/2 phosphorylation.
Conclusions
LL37 activated the ERK pathway to boost VEGF secretion from human pulp cells. Because of this angiogenic effect and its reported induction of pulp cell migration and antimicrobial activity against cariogenic bacteria, LL37 may be applicable as a pulp capping material.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antimicrobial Cationic Peptides</subject><subject>Bicuspid</subject><subject>Blotting, Western</subject><subject>Cathelicidins - pharmacology</subject><subject>Cell Culture Techniques</subject><subject>Cell Movement - drug effects</subject><subject>Cells, Cultured</subject><subject>Dental Pulp - cytology</subject><subject>Dental Pulp - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>ERK</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>LL37</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Phosphorylation</subject><subject>pulp cells</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Signal Transduction - drug effects</subject><subject>Up-Regulation</subject><subject>vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor A - drug effects</subject><issn>0143-2885</issn><issn>1365-2591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtOwzAQRS0EoqWw4AeQfyCtH7GdLFGVvohA4r2znGTaurhpFDei_XtCC53NHc3cM9JchG4p6dO2BhZWfcq4FGeoS1sJmIjpOeoSGvKARZHooCvvV4QQQTi9RB0mKCFU0i6apClX2JZFk4PH78l4hGFX1eC93ZTtHBdQbo3DVeMqnINzHm-X9aZZLHHy_IC9XZTGOVsurtHF3DgPN3_aQ2-j5HU4CdKn8XR4nwaWMyYCAApZTkJphAlzIUKloljmRRFlkIGKeQSch4xlIGJRUJCESU7V3IRhNI8Kznvo7ni3arI1FLqq7drUe_3_UmsYHA3f1sH-tKdE_2al26z0ISs9TWaHpiWCI2H9FnYnwtRfWiquhP54HGs6e-Hqk890zH8AlM5o_Q</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Khung, R.</creator><creator>Shiba, H.</creator><creator>Kajiya, M.</creator><creator>Kittaka, M.</creator><creator>Ouhara, K.</creator><creator>Takeda, K.</creator><creator>Mizuno, N.</creator><creator>Fujita, T.</creator><creator>Komatsuzawa, H.</creator><creator>Kurihara, H.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>201507</creationdate><title>LL37 induces VEGF expression in dental pulp cells through ERK signalling</title><author>Khung, R. ; Shiba, H. ; Kajiya, M. ; Kittaka, M. ; Ouhara, K. ; Takeda, K. ; Mizuno, N. ; Fujita, T. ; Komatsuzawa, H. ; Kurihara, H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3225-ee1ebc046a5a4c55477896cdd8bebe7938e33422be595d1e6026317fa448f8d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antimicrobial Cationic Peptides</topic><topic>Bicuspid</topic><topic>Blotting, Western</topic><topic>Cathelicidins - pharmacology</topic><topic>Cell Culture Techniques</topic><topic>Cell Movement - drug effects</topic><topic>Cells, Cultured</topic><topic>Dental Pulp - cytology</topic><topic>Dental Pulp - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>ERK</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>LL37</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Phosphorylation</topic><topic>pulp cells</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Signal Transduction - drug effects</topic><topic>Up-Regulation</topic><topic>vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor A - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khung, R.</creatorcontrib><creatorcontrib>Shiba, H.</creatorcontrib><creatorcontrib>Kajiya, M.</creatorcontrib><creatorcontrib>Kittaka, M.</creatorcontrib><creatorcontrib>Ouhara, K.</creatorcontrib><creatorcontrib>Takeda, K.</creatorcontrib><creatorcontrib>Mizuno, N.</creatorcontrib><creatorcontrib>Fujita, T.</creatorcontrib><creatorcontrib>Komatsuzawa, H.</creatorcontrib><creatorcontrib>Kurihara, H.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>International endodontic journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khung, R.</au><au>Shiba, H.</au><au>Kajiya, M.</au><au>Kittaka, M.</au><au>Ouhara, K.</au><au>Takeda, K.</au><au>Mizuno, N.</au><au>Fujita, T.</au><au>Komatsuzawa, H.</au><au>Kurihara, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LL37 induces VEGF expression in dental pulp cells through ERK signalling</atitle><jtitle>International endodontic journal</jtitle><addtitle>Int Endod J</addtitle><date>2015-07</date><risdate>2015</risdate><volume>48</volume><issue>7</issue><spage>673</spage><epage>679</epage><pages>673-679</pages><issn>0143-2885</issn><eissn>1365-2591</eissn><abstract>Aim
To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.
Methodology
Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was performed with MAPK or NF‐κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real‐time PCR, ELISA and Western blot, respectively. Data were analysed using t‐tests.
Results
LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre‐treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37‐induced ERK1/2 phosphorylation.
Conclusions
LL37 activated the ERK pathway to boost VEGF secretion from human pulp cells. Because of this angiogenic effect and its reported induction of pulp cell migration and antimicrobial activity against cariogenic bacteria, LL37 may be applicable as a pulp capping material.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25100161</pmid><doi>10.1111/iej.12365</doi><tpages>7</tpages></addata></record> |
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| ispartof | International endodontic journal, 2015-07, Vol.48 (7), p.673-679 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Anti-Bacterial Agents - pharmacology Antimicrobial Cationic Peptides Bicuspid Blotting, Western Cathelicidins - pharmacology Cell Culture Techniques Cell Movement - drug effects Cells, Cultured Dental Pulp - cytology Dental Pulp - drug effects Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay ERK Humans In Vitro Techniques LL37 MAP Kinase Signaling System - drug effects Neovascularization, Physiologic - drug effects Phosphorylation pulp cells Real-Time Polymerase Chain Reaction Signal Transduction - drug effects Up-Regulation vascular endothelial growth factor Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor A - drug effects |
| title | LL37 induces VEGF expression in dental pulp cells through ERK signalling |
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