MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions
Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix‐metalloproteinases (MMPs ‐1,‐3,‐9,‐13), IL‐1β and IL‐6, while it significantly increased MMP‐8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP‐8 induct...
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| Veröffentlicht in: | Journal of cellular physiology 2016-11, Vol.231 (11), p.2506-2516 |
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| creator | Bian, Fang Wang, Changjun Tukler-Henriksson, Johanna Pflugfelder, Stephen C. Camodeca, Caterina Nuti, Elisa Rossello, Armando Li, De-Quan de Paiva, Cintia S. |
| description | Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix‐metalloproteinases (MMPs ‐1,‐3,‐9,‐13), IL‐1β and IL‐6, while it significantly increased MMP‐8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP‐8 induction is responsible for some of the protective effects of Dex in CM, MMP‐8 knock out mice (MMP‐8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP‐8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP‐8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL‐6, CXCL1, and MMP‐1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP‐8KO mice. These results suggest that some of the anti‐inflammatory effects of Dex are mediated through increased MMP‐8 expression. J. Cell. Physiol. 231: 2506–2516, 2016. © 2016 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/jcp.25364 |
| format | Article |
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To investigate if MMP‐8 induction is responsible for some of the protective effects of Dex in CM, MMP‐8 knock out mice (MMP‐8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP‐8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP‐8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL‐6, CXCL1, and MMP‐1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP‐8KO mice. These results suggest that some of the anti‐inflammatory effects of Dex are mediated through increased MMP‐8 expression. J. Cell. Physiol. 231: 2506–2516, 2016. © 2016 Wiley Periodicals, Inc.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.25364</identifier><identifier>PMID: 26923552</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Alkalies ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Burns, Chemical - complications ; Burns, Chemical - drug therapy ; Burns, Chemical - enzymology ; Cornea - enzymology ; Cornea - pathology ; Desiccation ; Dexamethasone - pharmacology ; Dexamethasone - therapeutic use ; Disease Models, Animal ; Dry Eye Syndromes - complications ; Dry Eye Syndromes - enzymology ; Eye Burns - complications ; Eye Burns - drug therapy ; Eye Burns - enzymology ; Female ; Matrix Metalloproteinase 8 - deficiency ; Matrix Metalloproteinase 8 - genetics ; Matrix Metalloproteinase 8 - metabolism ; Matrix Metalloproteinase Inhibitors - pharmacology ; Matrix Metalloproteinase Inhibitors - therapeutic use ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophil Infiltration - drug effects ; Neutrophils - drug effects ; Neutrophils - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Stress, Physiological</subject><ispartof>Journal of cellular physiology, 2016-11, Vol.231 (11), p.2506-2516</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4474-b178a3461148d8d594f461b5a7e89759147e006fc772196fd1b77ab155c9d7b93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.25364$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.25364$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26923552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bian, Fang</creatorcontrib><creatorcontrib>Wang, Changjun</creatorcontrib><creatorcontrib>Tukler-Henriksson, Johanna</creatorcontrib><creatorcontrib>Pflugfelder, Stephen C.</creatorcontrib><creatorcontrib>Camodeca, Caterina</creatorcontrib><creatorcontrib>Nuti, Elisa</creatorcontrib><creatorcontrib>Rossello, Armando</creatorcontrib><creatorcontrib>Li, De-Quan</creatorcontrib><creatorcontrib>de Paiva, Cintia S.</creatorcontrib><title>MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions</title><title>Journal of cellular physiology</title><addtitle>J. Cell. Physiol</addtitle><description>Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix‐metalloproteinases (MMPs ‐1,‐3,‐9,‐13), IL‐1β and IL‐6, while it significantly increased MMP‐8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP‐8 induction is responsible for some of the protective effects of Dex in CM, MMP‐8 knock out mice (MMP‐8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP‐8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP‐8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL‐6, CXCL1, and MMP‐1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP‐8KO mice. These results suggest that some of the anti‐inflammatory effects of Dex are mediated through increased MMP‐8 expression. J. Cell. Physiol. 231: 2506–2516, 2016. © 2016 Wiley Periodicals, Inc.</description><subject>Alkalies</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Burns, Chemical - complications</subject><subject>Burns, Chemical - drug therapy</subject><subject>Burns, Chemical - enzymology</subject><subject>Cornea - enzymology</subject><subject>Cornea - pathology</subject><subject>Desiccation</subject><subject>Dexamethasone - pharmacology</subject><subject>Dexamethasone - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Dry Eye Syndromes - complications</subject><subject>Dry Eye Syndromes - enzymology</subject><subject>Eye Burns - complications</subject><subject>Eye Burns - drug therapy</subject><subject>Eye Burns - enzymology</subject><subject>Female</subject><subject>Matrix Metalloproteinase 8 - deficiency</subject><subject>Matrix Metalloproteinase 8 - genetics</subject><subject>Matrix Metalloproteinase 8 - metabolism</subject><subject>Matrix Metalloproteinase Inhibitors - pharmacology</subject><subject>Matrix Metalloproteinase Inhibitors - therapeutic use</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neutrophil Infiltration - drug effects</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Stress, Physiological</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU1PGzEUtKpWJaU99A9UlnrhsmDv-vOCBMtHqULKIcAJWd5dL3HY2MHetOy_r0loBD09229m3vMMAF8x2scI5Qfzermf04KRd2CEkeQZYTR_D0aphzNJCd4Bn2KcI4SkLIqPYCdnMi8ozUfg7vLyKhPwIsIy2N7WuoOtD_DEPOmF6Wc6emfgdGaCXg7QOnjUPejOZser4EwDS5-KjvDaNSaRwgBPB5NeXZO0vIufwYdWd9F8eam74PrsdFr-yMa_zi_Ko3FWE8JJVmEudEEYxkQ0oqGStOlSUc2NkJxKTLhBiLU15zmWrG1wxbmuMKW1bHgli11wuNFdrqqFaWrj-qA7tQx2ocOgvLbqbcfZmbr3vxWRhEkpksDei0DwjysTe7WwsTZdp53xq6iwQEQwgdjzrO__Qec-uZG-t0bh5DchCfXt9UbbVf45nwAHG8Af25lh28dIPUeqUqRqHan6WV6tD4mRbRg29uZpy9DhQTFecKpuJ-eKTM5uxieTGzUt_gLtFqDc</recordid><startdate>201611</startdate><enddate>201611</enddate><creator>Bian, Fang</creator><creator>Wang, Changjun</creator><creator>Tukler-Henriksson, Johanna</creator><creator>Pflugfelder, Stephen C.</creator><creator>Camodeca, Caterina</creator><creator>Nuti, Elisa</creator><creator>Rossello, Armando</creator><creator>Li, De-Quan</creator><creator>de Paiva, Cintia S.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201611</creationdate><title>MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions</title><author>Bian, Fang ; Wang, Changjun ; Tukler-Henriksson, Johanna ; Pflugfelder, Stephen C. ; Camodeca, Caterina ; Nuti, Elisa ; Rossello, Armando ; Li, De-Quan ; de Paiva, Cintia S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4474-b178a3461148d8d594f461b5a7e89759147e006fc772196fd1b77ab155c9d7b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alkalies</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Burns, Chemical - complications</topic><topic>Burns, Chemical - drug therapy</topic><topic>Burns, Chemical - enzymology</topic><topic>Cornea - enzymology</topic><topic>Cornea - pathology</topic><topic>Desiccation</topic><topic>Dexamethasone - pharmacology</topic><topic>Dexamethasone - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Dry Eye Syndromes - complications</topic><topic>Dry Eye Syndromes - enzymology</topic><topic>Eye Burns - complications</topic><topic>Eye Burns - drug therapy</topic><topic>Eye Burns - enzymology</topic><topic>Female</topic><topic>Matrix Metalloproteinase 8 - deficiency</topic><topic>Matrix Metalloproteinase 8 - genetics</topic><topic>Matrix Metalloproteinase 8 - metabolism</topic><topic>Matrix Metalloproteinase Inhibitors - pharmacology</topic><topic>Matrix Metalloproteinase Inhibitors - therapeutic use</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neutrophil Infiltration - drug effects</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Stress, Physiological</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bian, Fang</creatorcontrib><creatorcontrib>Wang, Changjun</creatorcontrib><creatorcontrib>Tukler-Henriksson, Johanna</creatorcontrib><creatorcontrib>Pflugfelder, Stephen C.</creatorcontrib><creatorcontrib>Camodeca, Caterina</creatorcontrib><creatorcontrib>Nuti, Elisa</creatorcontrib><creatorcontrib>Rossello, Armando</creatorcontrib><creatorcontrib>Li, De-Quan</creatorcontrib><creatorcontrib>de Paiva, Cintia S.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bian, Fang</au><au>Wang, Changjun</au><au>Tukler-Henriksson, Johanna</au><au>Pflugfelder, Stephen C.</au><au>Camodeca, Caterina</au><au>Nuti, Elisa</au><au>Rossello, Armando</au><au>Li, De-Quan</au><au>de Paiva, Cintia S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J. Cell. Physiol</addtitle><date>2016-11</date><risdate>2016</risdate><volume>231</volume><issue>11</issue><spage>2506</spage><epage>2516</epage><pages>2506-2516</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix‐metalloproteinases (MMPs ‐1,‐3,‐9,‐13), IL‐1β and IL‐6, while it significantly increased MMP‐8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP‐8 induction is responsible for some of the protective effects of Dex in CM, MMP‐8 knock out mice (MMP‐8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP‐8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP‐8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL‐6, CXCL1, and MMP‐1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP‐8KO mice. These results suggest that some of the anti‐inflammatory effects of Dex are mediated through increased MMP‐8 expression. J. Cell. Physiol. 231: 2506–2516, 2016. © 2016 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26923552</pmid><doi>10.1002/jcp.25364</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alkalies Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Burns, Chemical - complications Burns, Chemical - drug therapy Burns, Chemical - enzymology Cornea - enzymology Cornea - pathology Desiccation Dexamethasone - pharmacology Dexamethasone - therapeutic use Disease Models, Animal Dry Eye Syndromes - complications Dry Eye Syndromes - enzymology Eye Burns - complications Eye Burns - drug therapy Eye Burns - enzymology Female Matrix Metalloproteinase 8 - deficiency Matrix Metalloproteinase 8 - genetics Matrix Metalloproteinase 8 - metabolism Matrix Metalloproteinase Inhibitors - pharmacology Matrix Metalloproteinase Inhibitors - therapeutic use Mice, Inbred C57BL Mice, Knockout Neutrophil Infiltration - drug effects Neutrophils - drug effects Neutrophils - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Stress, Physiological |
| title | MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions |
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