Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts

Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of...

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Veröffentlicht in:Journal of periodontal research 2008-06, Vol.43 (3), p.255-260
Hauptverfasser: Cury, P. R., Canavez, F., De Araújo, V. C., Furuse, C., De Araújo, N. S.
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container_end_page 260
container_issue 3
container_start_page 255
container_title Journal of periodontal research
container_volume 43
creator Cury, P. R.
Canavez, F.
De Araújo, V. C.
Furuse, C.
De Araújo, N. S.
description Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Material and Methods:  Fibroblasts were stimulated for 48 h with 10−4 or 10−9 m Substance P; untreated fibroblasts served as controls. The expression of MMP‐1, ‐2, ‐3, ‐7 and ‐11 and of TIMP‐1 and ‐2 was evaluated using real‐time polymerase chain reaction and western blotting. Results:  There was a significant, concentration‐dependent stimulatory effect of Substance P on MMP‐1, ‐2, ‐3 and ‐7 and TIMP‐2 gene expression (p 
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R. ; Canavez, F. ; De Araújo, V. C. ; Furuse, C. ; De Araújo, N. S.</creator><creatorcontrib>Cury, P. R. ; Canavez, F. ; De Araújo, V. C. ; Furuse, C. ; De Araújo, N. S.</creatorcontrib><description>Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Material and Methods:  Fibroblasts were stimulated for 48 h with 10−4 or 10−9 m Substance P; untreated fibroblasts served as controls. The expression of MMP‐1, ‐2, ‐3, ‐7 and ‐11 and of TIMP‐1 and ‐2 was evaluated using real‐time polymerase chain reaction and western blotting. Results:  There was a significant, concentration‐dependent stimulatory effect of Substance P on MMP‐1, ‐2, ‐3 and ‐7 and TIMP‐2 gene expression (p &lt; 0.05), and a probable effect on MMP‐11 (p = 0.06). At the higher concentration (10−4 m Substance P), MMP‐1, ‐2, ‐3, ‐7 and ‐11 and TIMP‐2 showed the greatest up‐regulation; at the lower concentration (10−9 m Substance P), MMP‐1, ‐3 and ‐7 and TIMP‐2 exhibited diminished up‐regulation, with MMP‐2 and ‐11 showing down‐regulation (p &lt; 0.05). Expression of TIMP‐1 was not affected by Substance P (p &gt; 0.05). Western blotting confirmed that Substance P up‐regulated MMP‐1, ‐2, ‐3 and ‐11 and TIMP‐2. MMP‐1, ‐3 and ‐11 and TIMP‐2 showed greater up‐regulation at the higher Substance P concentration and diminished up‐regulation at the lower concentration. MMP‐2 was up‐regulated to a similar degree at both Substance P concentrations. Conclusion:  In gingival fibroblast cells, Substance P at the higher concentration (10−4 m) induced greater up‐regulation of MMP‐1, ‐3 and ‐11 and TIMP‐2 expression, but at the lower concentration (10−9 m) induced diminished up‐regulation, which may represent a mechanism for modulating periodontal breakdown.</description><identifier>ISSN: 0022-3484</identifier><identifier>EISSN: 1600-0765</identifier><identifier>DOI: 10.1111/j.1600-0765.2007.01022.x</identifier><identifier>PMID: 18179473</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Blotting, Western ; Cells, Cultured ; Dentistry ; Dose-Response Relationship, Drug ; Enzyme Activation ; Fibroblasts - enzymology ; Gene Expression ; Gingiva - cytology ; Gingiva - enzymology ; gingival fibroblasts ; Humans ; matrix metalloproteinase ; Matrix Metalloproteinases - biosynthesis ; Medical sciences ; Otorhinolaryngology. Stomatology ; Polymerase Chain Reaction ; Statistics, Nonparametric ; Substance P ; Substance P - administration &amp; dosage ; Substance P - pharmacology ; Substance P - physiology ; tissue inhibitor of metalloproteinase ; Tissue Inhibitor of Metalloproteinases - biosynthesis ; Up-Regulation</subject><ispartof>Journal of periodontal research, 2008-06, Vol.43 (3), p.255-260</ispartof><rights>2007 The Authors. 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R.</creatorcontrib><creatorcontrib>Canavez, F.</creatorcontrib><creatorcontrib>De Araújo, V. C.</creatorcontrib><creatorcontrib>Furuse, C.</creatorcontrib><creatorcontrib>De Araújo, N. S.</creatorcontrib><title>Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts</title><title>Journal of periodontal research</title><addtitle>J Periodontal Res</addtitle><description>Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Material and Methods:  Fibroblasts were stimulated for 48 h with 10−4 or 10−9 m Substance P; untreated fibroblasts served as controls. The expression of MMP‐1, ‐2, ‐3, ‐7 and ‐11 and of TIMP‐1 and ‐2 was evaluated using real‐time polymerase chain reaction and western blotting. Results:  There was a significant, concentration‐dependent stimulatory effect of Substance P on MMP‐1, ‐2, ‐3 and ‐7 and TIMP‐2 gene expression (p &lt; 0.05), and a probable effect on MMP‐11 (p = 0.06). At the higher concentration (10−4 m Substance P), MMP‐1, ‐2, ‐3, ‐7 and ‐11 and TIMP‐2 showed the greatest up‐regulation; at the lower concentration (10−9 m Substance P), MMP‐1, ‐3 and ‐7 and TIMP‐2 exhibited diminished up‐regulation, with MMP‐2 and ‐11 showing down‐regulation (p &lt; 0.05). Expression of TIMP‐1 was not affected by Substance P (p &gt; 0.05). Western blotting confirmed that Substance P up‐regulated MMP‐1, ‐2, ‐3 and ‐11 and TIMP‐2. MMP‐1, ‐3 and ‐11 and TIMP‐2 showed greater up‐regulation at the higher Substance P concentration and diminished up‐regulation at the lower concentration. MMP‐2 was up‐regulated to a similar degree at both Substance P concentrations. Conclusion:  In gingival fibroblast cells, Substance P at the higher concentration (10−4 m) induced greater up‐regulation of MMP‐1, ‐3 and ‐11 and TIMP‐2 expression, but at the lower concentration (10−9 m) induced diminished up‐regulation, which may represent a mechanism for modulating periodontal breakdown.</description><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Dentistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation</subject><subject>Fibroblasts - enzymology</subject><subject>Gene Expression</subject><subject>Gingiva - cytology</subject><subject>Gingiva - enzymology</subject><subject>gingival fibroblasts</subject><subject>Humans</subject><subject>matrix metalloproteinase</subject><subject>Matrix Metalloproteinases - biosynthesis</subject><subject>Medical sciences</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Polymerase Chain Reaction</subject><subject>Statistics, Nonparametric</subject><subject>Substance P</subject><subject>Substance P - administration &amp; dosage</subject><subject>Substance P - pharmacology</subject><subject>Substance P - physiology</subject><subject>tissue inhibitor of metalloproteinase</subject><subject>Tissue Inhibitor of Metalloproteinases - biosynthesis</subject><subject>Up-Regulation</subject><issn>0022-3484</issn><issn>1600-0765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxiMEokvhFZAvcEuwnTh_DhxQKVuqChAFcbQce7LrxUkWjwPpc_DCON3VInHCF9szv88zni9JCKMZi-vVLmMlpSmtSpFxSquMMsp5Nj9IVqfEw2RFYzDNi7o4S54g7mi8l1XzODljNauaospXye_bqcWgBg3kE_GwmZwKgCRsgcC894Box4GMHelV8HYmPQTl3Lj3YwA7KIysGgwJFnECYoetbW0YPd5L_mVjnujJhcmDIdupVwPZ2GFjfypHOtv6sXUKAz5NHnXKITw77ufJ13eXXy6u0puP6_cXb25SXeSCp5yb3PCcVaCNbgwwoVlLoS6VAVOLqmh0yxsoFDetEiJ-1xRciJJ2hdClpvl58vLwbuzwxwQYZG9Rg3NqgHFCWTZMNGWTR7A-gNqPiB46ufe2V_5OMioXQ-ROLnOXy9zlYoi8N0TOUfr8WGNqezB_hUcHIvDiCCjUynU-emHxxHGaM1oUPHKvD9wv6-DuvxuQ158vl1PUpwe9xQDzSa_8d1lWeSXktw9reXt91azfikry_A_GX7n7</recordid><startdate>200806</startdate><enddate>200806</enddate><creator>Cury, P. R.</creator><creator>Canavez, F.</creator><creator>De Araújo, V. C.</creator><creator>Furuse, C.</creator><creator>De Araújo, N. S.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><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>200806</creationdate><title>Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts</title><author>Cury, P. R. ; Canavez, F. ; De Araújo, V. C. ; Furuse, C. ; De Araújo, N. S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4352-22d3d2317ecdc9de15c1b0e86aded85749cb29e4a2dba55473d425560f45c6c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cells, Cultured</topic><topic>Dentistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation</topic><topic>Fibroblasts - enzymology</topic><topic>Gene Expression</topic><topic>Gingiva - cytology</topic><topic>Gingiva - enzymology</topic><topic>gingival fibroblasts</topic><topic>Humans</topic><topic>matrix metalloproteinase</topic><topic>Matrix Metalloproteinases - biosynthesis</topic><topic>Medical sciences</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Polymerase Chain Reaction</topic><topic>Statistics, Nonparametric</topic><topic>Substance P</topic><topic>Substance P - administration &amp; dosage</topic><topic>Substance P - pharmacology</topic><topic>Substance P - physiology</topic><topic>tissue inhibitor of metalloproteinase</topic><topic>Tissue Inhibitor of Metalloproteinases - biosynthesis</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cury, P. R.</creatorcontrib><creatorcontrib>Canavez, F.</creatorcontrib><creatorcontrib>De Araújo, V. C.</creatorcontrib><creatorcontrib>Furuse, C.</creatorcontrib><creatorcontrib>De Araújo, N. S.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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>Journal of periodontal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cury, P. R.</au><au>Canavez, F.</au><au>De Araújo, V. C.</au><au>Furuse, C.</au><au>De Araújo, N. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts</atitle><jtitle>Journal of periodontal research</jtitle><addtitle>J Periodontal Res</addtitle><date>2008-06</date><risdate>2008</risdate><volume>43</volume><issue>3</issue><spage>255</spage><epage>260</epage><pages>255-260</pages><issn>0022-3484</issn><eissn>1600-0765</eissn><abstract>Background and Objective:  Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Material and Methods:  Fibroblasts were stimulated for 48 h with 10−4 or 10−9 m Substance P; untreated fibroblasts served as controls. The expression of MMP‐1, ‐2, ‐3, ‐7 and ‐11 and of TIMP‐1 and ‐2 was evaluated using real‐time polymerase chain reaction and western blotting. Results:  There was a significant, concentration‐dependent stimulatory effect of Substance P on MMP‐1, ‐2, ‐3 and ‐7 and TIMP‐2 gene expression (p &lt; 0.05), and a probable effect on MMP‐11 (p = 0.06). At the higher concentration (10−4 m Substance P), MMP‐1, ‐2, ‐3, ‐7 and ‐11 and TIMP‐2 showed the greatest up‐regulation; at the lower concentration (10−9 m Substance P), MMP‐1, ‐3 and ‐7 and TIMP‐2 exhibited diminished up‐regulation, with MMP‐2 and ‐11 showing down‐regulation (p &lt; 0.05). Expression of TIMP‐1 was not affected by Substance P (p &gt; 0.05). Western blotting confirmed that Substance P up‐regulated MMP‐1, ‐2, ‐3 and ‐11 and TIMP‐2. MMP‐1, ‐3 and ‐11 and TIMP‐2 showed greater up‐regulation at the higher Substance P concentration and diminished up‐regulation at the lower concentration. MMP‐2 was up‐regulated to a similar degree at both Substance P concentrations. Conclusion:  In gingival fibroblast cells, Substance P at the higher concentration (10−4 m) induced greater up‐regulation of MMP‐1, ‐3 and ‐11 and TIMP‐2 expression, but at the lower concentration (10−9 m) induced diminished up‐regulation, which may represent a mechanism for modulating periodontal breakdown.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18179473</pmid><doi>10.1111/j.1600-0765.2007.01022.x</doi><tpages>6</tpages></addata></record>
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subjects Biological and medical sciences
Blotting, Western
Cells, Cultured
Dentistry
Dose-Response Relationship, Drug
Enzyme Activation
Fibroblasts - enzymology
Gene Expression
Gingiva - cytology
Gingiva - enzymology
gingival fibroblasts
Humans
matrix metalloproteinase
Matrix Metalloproteinases - biosynthesis
Medical sciences
Otorhinolaryngology. Stomatology
Polymerase Chain Reaction
Statistics, Nonparametric
Substance P
Substance P - administration & dosage
Substance P - pharmacology
Substance P - physiology
tissue inhibitor of metalloproteinase
Tissue Inhibitor of Metalloproteinases - biosynthesis
Up-Regulation
title Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts
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