Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice
Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clin...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2008-06, Vol.180 (12), p.8361-8368 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 8368 |
|---|---|
| container_issue | 12 |
| container_start_page | 8361 |
| container_title | The Journal of immunology (1950) |
| container_volume | 180 |
| creator | Kojima, Fumiaki Kapoor, Mohit Yang, Lihua Fleishaker, Erica L Ward, Martin R Monrad, Seetha U Kottangada, Ponnappa C Pace, Charles Q Clark, James A Woodward, Jerold G Crofford, Leslie J |
| description | Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. |
| doi_str_mv | 10.4049/jimmunol.180.12.8361 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2435291</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20725619</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-deb308c4ab7fb1727a8af14cd444af42b08fe3c8142780ae962f7b23095c5d8f3</originalsourceid><addsrcrecordid>eNpVkc1u1DAUhS0EokPhDRDyCrHJYDvO3wZpNJQ2UvlRC2vLcW4mrhJ7sJ2J5sV4PhzNAGVlW_e751jnIPSakjUnvHr_oMdxMnZY05KsKVuXaU6foBXNMpLkOcmfohUhjCW0yIsL9ML7B0JIThh_ji5ombE0JekK_foIHaigD4CvwYCTQVuDbYclvplG6-SA68UH8B34vTUecO3xxnurtAzQ4lmHPsJ30E4qPmujdAtGAZamxfdwAKfDcRHc2mGQOzBJbU7oxoU-DrXH2uDPWjnr7Rj9vsVLkLshCsTBFb4_mtBLDwnFX6ZhWFB4iZ51cvDw6nxeoh-frr5vb5Lbr9f1dnObKF6QkLTQpKRUXDZF19CCFbKUHeWq5ZzLjrOGlB2kqqScFSWRUOWsKxqWkipTWVt26SX6cNLdT80IrQITYiRi7_Qo3VFYqcX_E6N7sbMHwXiasYpGgbdnAWd_TuCDGLVXEKMwYCcvGClYltMqgvwELjl4B91fE0rEUrj4U7iIhQvKxFJ4XHvz-IP_ls4NR-DdCej1rp-1A-FjyEPEqZjn-bHWbzPlu6w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20725619</pqid></control><display><type>article</type><title>Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice</title><source>MEDLINE</source><source>Free E-Journal (出版社公開部分のみ）</source><source>Alma/SFX Local Collection</source><creator>Kojima, Fumiaki ; Kapoor, Mohit ; Yang, Lihua ; Fleishaker, Erica L ; Ward, Martin R ; Monrad, Seetha U ; Kottangada, Ponnappa C ; Pace, Charles Q ; Clark, James A ; Woodward, Jerold G ; Crofford, Leslie J</creator><creatorcontrib>Kojima, Fumiaki ; Kapoor, Mohit ; Yang, Lihua ; Fleishaker, Erica L ; Ward, Martin R ; Monrad, Seetha U ; Kottangada, Ponnappa C ; Pace, Charles Q ; Clark, James A ; Woodward, Jerold G ; Crofford, Leslie J</creatorcontrib><description>Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.180.12.8361</identifier><identifier>PMID: 18523303</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Arthritis, Experimental - enzymology ; Arthritis, Experimental - genetics ; Arthritis, Experimental - immunology ; Arthritis, Experimental - therapy ; Cattle ; Collagen Type II - administration & dosage ; Collagen Type II - immunology ; Cyclooxygenase 1 - deficiency ; Cyclooxygenase 1 - genetics ; Cyclooxygenase 1 - physiology ; Cyclooxygenase 2 - biosynthesis ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - physiology ; Female ; Gene Deletion ; Genetic Carrier Screening ; Immunoglobulin G - biosynthesis ; Immunoglobulin G - blood ; Immunoglobulin G - physiology ; Immunoglobulin M - biosynthesis ; Incidence ; Male ; Membrane Proteins - deficiency ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Mice ; Mice, Inbred DBA ; Mice, Knockout ; Microsomes - enzymology ; RNA, Messenger - biosynthesis ; Severity of Illness Index</subject><ispartof>The Journal of immunology (1950), 2008-06, Vol.180 (12), p.8361-8368</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-deb308c4ab7fb1727a8af14cd444af42b08fe3c8142780ae962f7b23095c5d8f3</citedby><cites>FETCH-LOGICAL-c470t-deb308c4ab7fb1727a8af14cd444af42b08fe3c8142780ae962f7b23095c5d8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18523303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kojima, Fumiaki</creatorcontrib><creatorcontrib>Kapoor, Mohit</creatorcontrib><creatorcontrib>Yang, Lihua</creatorcontrib><creatorcontrib>Fleishaker, Erica L</creatorcontrib><creatorcontrib>Ward, Martin R</creatorcontrib><creatorcontrib>Monrad, Seetha U</creatorcontrib><creatorcontrib>Kottangada, Ponnappa C</creatorcontrib><creatorcontrib>Pace, Charles Q</creatorcontrib><creatorcontrib>Clark, James A</creatorcontrib><creatorcontrib>Woodward, Jerold G</creatorcontrib><creatorcontrib>Crofford, Leslie J</creatorcontrib><title>Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis.</description><subject>Animals</subject><subject>Arthritis, Experimental - enzymology</subject><subject>Arthritis, Experimental - genetics</subject><subject>Arthritis, Experimental - immunology</subject><subject>Arthritis, Experimental - therapy</subject><subject>Cattle</subject><subject>Collagen Type II - administration & dosage</subject><subject>Collagen Type II - immunology</subject><subject>Cyclooxygenase 1 - deficiency</subject><subject>Cyclooxygenase 1 - genetics</subject><subject>Cyclooxygenase 1 - physiology</subject><subject>Cyclooxygenase 2 - biosynthesis</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - physiology</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Genetic Carrier Screening</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - physiology</subject><subject>Immunoglobulin M - biosynthesis</subject><subject>Incidence</subject><subject>Male</subject><subject>Membrane Proteins - deficiency</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>Mice, Knockout</subject><subject>Microsomes - enzymology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Severity of Illness Index</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1DAUhS0EokPhDRDyCrHJYDvO3wZpNJQ2UvlRC2vLcW4mrhJ7sJ2J5sV4PhzNAGVlW_e751jnIPSakjUnvHr_oMdxMnZY05KsKVuXaU6foBXNMpLkOcmfohUhjCW0yIsL9ML7B0JIThh_ji5ombE0JekK_foIHaigD4CvwYCTQVuDbYclvplG6-SA68UH8B34vTUecO3xxnurtAzQ4lmHPsJ30E4qPmujdAtGAZamxfdwAKfDcRHc2mGQOzBJbU7oxoU-DrXH2uDPWjnr7Rj9vsVLkLshCsTBFb4_mtBLDwnFX6ZhWFB4iZ51cvDw6nxeoh-frr5vb5Lbr9f1dnObKF6QkLTQpKRUXDZF19CCFbKUHeWq5ZzLjrOGlB2kqqScFSWRUOWsKxqWkipTWVt26SX6cNLdT80IrQITYiRi7_Qo3VFYqcX_E6N7sbMHwXiasYpGgbdnAWd_TuCDGLVXEKMwYCcvGClYltMqgvwELjl4B91fE0rEUrj4U7iIhQvKxFJ4XHvz-IP_ls4NR-DdCej1rp-1A-FjyEPEqZjn-bHWbzPlu6w</recordid><startdate>20080615</startdate><enddate>20080615</enddate><creator>Kojima, Fumiaki</creator><creator>Kapoor, Mohit</creator><creator>Yang, Lihua</creator><creator>Fleishaker, Erica L</creator><creator>Ward, Martin R</creator><creator>Monrad, Seetha U</creator><creator>Kottangada, Ponnappa C</creator><creator>Pace, Charles Q</creator><creator>Clark, James A</creator><creator>Woodward, Jerold G</creator><creator>Crofford, Leslie J</creator><general>Am Assoc Immnol</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>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20080615</creationdate><title>Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice</title><author>Kojima, Fumiaki ; Kapoor, Mohit ; Yang, Lihua ; Fleishaker, Erica L ; Ward, Martin R ; Monrad, Seetha U ; Kottangada, Ponnappa C ; Pace, Charles Q ; Clark, James A ; Woodward, Jerold G ; Crofford, Leslie J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-deb308c4ab7fb1727a8af14cd444af42b08fe3c8142780ae962f7b23095c5d8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Arthritis, Experimental - enzymology</topic><topic>Arthritis, Experimental - genetics</topic><topic>Arthritis, Experimental - immunology</topic><topic>Arthritis, Experimental - therapy</topic><topic>Cattle</topic><topic>Collagen Type II - administration & dosage</topic><topic>Collagen Type II - immunology</topic><topic>Cyclooxygenase 1 - deficiency</topic><topic>Cyclooxygenase 1 - genetics</topic><topic>Cyclooxygenase 1 - physiology</topic><topic>Cyclooxygenase 2 - biosynthesis</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - physiology</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Genetic Carrier Screening</topic><topic>Immunoglobulin G - biosynthesis</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - physiology</topic><topic>Immunoglobulin M - biosynthesis</topic><topic>Incidence</topic><topic>Male</topic><topic>Membrane Proteins - deficiency</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>Mice, Knockout</topic><topic>Microsomes - enzymology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Severity of Illness Index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kojima, Fumiaki</creatorcontrib><creatorcontrib>Kapoor, Mohit</creatorcontrib><creatorcontrib>Yang, Lihua</creatorcontrib><creatorcontrib>Fleishaker, Erica L</creatorcontrib><creatorcontrib>Ward, Martin R</creatorcontrib><creatorcontrib>Monrad, Seetha U</creatorcontrib><creatorcontrib>Kottangada, Ponnappa C</creatorcontrib><creatorcontrib>Pace, Charles Q</creatorcontrib><creatorcontrib>Clark, James A</creatorcontrib><creatorcontrib>Woodward, Jerold G</creatorcontrib><creatorcontrib>Crofford, Leslie J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kojima, Fumiaki</au><au>Kapoor, Mohit</au><au>Yang, Lihua</au><au>Fleishaker, Erica L</au><au>Ward, Martin R</au><au>Monrad, Seetha U</au><au>Kottangada, Ponnappa C</au><au>Pace, Charles Q</au><au>Clark, James A</au><au>Woodward, Jerold G</au><au>Crofford, Leslie J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2008-06-15</date><risdate>2008</risdate><volume>180</volume><issue>12</issue><spage>8361</spage><epage>8368</epage><pages>8361-8368</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>18523303</pmid><doi>10.4049/jimmunol.180.12.8361</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2008-06, Vol.180 (12), p.8361-8368 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2435291 |
| source | MEDLINE; Free E-Journal (出版社公開部分のみ）; Alma/SFX Local Collection |
| subjects | Animals Arthritis, Experimental - enzymology Arthritis, Experimental - genetics Arthritis, Experimental - immunology Arthritis, Experimental - therapy Cattle Collagen Type II - administration & dosage Collagen Type II - immunology Cyclooxygenase 1 - deficiency Cyclooxygenase 1 - genetics Cyclooxygenase 1 - physiology Cyclooxygenase 2 - biosynthesis Cyclooxygenase 2 - genetics Cyclooxygenase 2 - physiology Female Gene Deletion Genetic Carrier Screening Immunoglobulin G - biosynthesis Immunoglobulin G - blood Immunoglobulin G - physiology Immunoglobulin M - biosynthesis Incidence Male Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Inbred DBA Mice, Knockout Microsomes - enzymology RNA, Messenger - biosynthesis Severity of Illness Index |
| title | Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T08%3A20%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Defective%20Generation%20of%20a%20Humoral%20Immune%20Response%20Is%20Associated%20with%20a%20Reduced%20Incidence%20and%20Severity%20of%20Collagen-Induced%20Arthritis%20in%20Microsomal%20Prostaglandin%20E%20Synthase-1%20Null%20Mice&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Kojima,%20Fumiaki&rft.date=2008-06-15&rft.volume=180&rft.issue=12&rft.spage=8361&rft.epage=8368&rft.pages=8361-8368&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.180.12.8361&rft_dat=%3Cproquest_pubme%3E20725619%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20725619&rft_id=info:pmid/18523303&rfr_iscdi=true |