Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent
Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-05, Vol.6 (5), p.e19962-e19962 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e19962 |
|---|---|
| container_issue | 5 |
| container_start_page | e19962 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Roescher, Nienke Vosters, Jelle L Yin, Hongen Illei, Gabor G Tak, Paul P Chiorini, John A |
| description | Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.
A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).
Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA.
Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG. |
| doi_str_mv | 10.1371/journal.pone.0019962 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1294916432</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_e7e94273db88427781e2ce01653f7fed</doaj_id><sourcerecordid>2898626141</sourcerecordid><originalsourceid>FETCH-LOGICAL-c525t-3e73c12708479a75b77fe65abe108a883aec41e962f3d7f679b64d46234b32ea3</originalsourceid><addsrcrecordid>eNptUstu1TAQjRCIPuAPEFhi0VUufsWPDRIqBSoVugDWluNM0lwSO9gJ0v0xfqA_hstNqxaxmpHnnDNzrFMULwjeECbJm21YorfDZgoeNhgTrQV9VBwSzWgpKGaP7_UHxVFKW4wrpoR4WhxQUimtpDosurO2BTej0KIUhqUeAJ2fvvtcEhQ8sujr9vp3F8GfJJR2volhhHLofwCarsCHeTcB6j36cvkejb3LfUJNn8AmQGm2HaAGJvAN-PlZ8aS1Q4Lnaz0uvn84-3b6qby4_JgXXpSuotVcMpDMESqx4lJbWdVStiAqWwPByirFLDhOIFttWSNbIXUteMMFZbxmFCw7Ll7tdachJLP-UTKEaq6J4IxmxPke0QS7NVPsRxt3Jtje_H0IsTM2zr0bwIAEzalkTa1UrlIRoA4wERVr811N1nq7blvqERqXjUY7PBB9OPH9lenCL8OwZhzzLHCyCsTwc4E0m7FPDobBeghLMkpISRnVOCNf_4P8vzm-R7kYUorQ3t1CsLmJzS3L3MTGrLHJtJf3fdyRbnPC_gA6DcAp</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1294916432</pqid></control><display><type>article</type><title>Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Roescher, Nienke ; Vosters, Jelle L ; Yin, Hongen ; Illei, Gabor G ; Tak, Paul P ; Chiorini, John A</creator><contributor>Shi, Songtao</contributor><creatorcontrib>Roescher, Nienke ; Vosters, Jelle L ; Yin, Hongen ; Illei, Gabor G ; Tak, Paul P ; Chiorini, John A ; Shi, Songtao</creatorcontrib><description>Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.
A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).
Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA.
Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0019962</identifier><identifier>PMID: 21589878</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Age ; Animals ; Antigens ; Biology ; Biopsy ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell adhesion ; Cell adhesion & migration ; Cell migration ; Clinical trials ; Cytokines ; Dendritic cells ; Diabetes ; Diabetes mellitus ; Disease ; Female ; Gene therapy ; Glands ; Immune system ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Immunology ; Inflammation ; Intercellular adhesion molecule 1 ; Intercellular Adhesion Molecule-1 - metabolism ; Leukocyte migration ; LFA-1 antigen ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Medicine ; Mice ; Mice, Inbred NOD ; Multiple sclerosis ; Patients ; Physiology ; Rheumatoid arthritis ; Rheumatology ; Rodents ; Saliva - secretion ; Salivary glands ; Sjogren's syndrome ; Sjogren's Syndrome - immunology ; Sjogren's Syndrome - metabolism ; Tumor necrosis factor-TNF ; Viruses</subject><ispartof>PloS one, 2011-05, Vol.6 (5), p.e19962-e19962</ispartof><rights>2011. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-3e73c12708479a75b77fe65abe108a883aec41e962f3d7f679b64d46234b32ea3</citedby><cites>FETCH-LOGICAL-c525t-3e73c12708479a75b77fe65abe108a883aec41e962f3d7f679b64d46234b32ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093404/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093404/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21589878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Shi, Songtao</contributor><creatorcontrib>Roescher, Nienke</creatorcontrib><creatorcontrib>Vosters, Jelle L</creatorcontrib><creatorcontrib>Yin, Hongen</creatorcontrib><creatorcontrib>Illei, Gabor G</creatorcontrib><creatorcontrib>Tak, Paul P</creatorcontrib><creatorcontrib>Chiorini, John A</creatorcontrib><title>Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.
A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).
Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA.
Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG.</description><subject>Acids</subject><subject>Age</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biology</subject><subject>Biopsy</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Disease</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Glands</subject><subject>Immune system</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Intercellular adhesion molecule 1</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Leukocyte migration</subject><subject>LFA-1 antigen</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Multiple sclerosis</subject><subject>Patients</subject><subject>Physiology</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatology</subject><subject>Rodents</subject><subject>Saliva - secretion</subject><subject>Salivary glands</subject><subject>Sjogren's syndrome</subject><subject>Sjogren's Syndrome - immunology</subject><subject>Sjogren's Syndrome - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1TAQjRCIPuAPEFhi0VUufsWPDRIqBSoVugDWluNM0lwSO9gJ0v0xfqA_hstNqxaxmpHnnDNzrFMULwjeECbJm21YorfDZgoeNhgTrQV9VBwSzWgpKGaP7_UHxVFKW4wrpoR4WhxQUimtpDosurO2BTej0KIUhqUeAJ2fvvtcEhQ8sujr9vp3F8GfJJR2volhhHLofwCarsCHeTcB6j36cvkejb3LfUJNn8AmQGm2HaAGJvAN-PlZ8aS1Q4Lnaz0uvn84-3b6qby4_JgXXpSuotVcMpDMESqx4lJbWdVStiAqWwPByirFLDhOIFttWSNbIXUteMMFZbxmFCw7Ll7tdachJLP-UTKEaq6J4IxmxPke0QS7NVPsRxt3Jtje_H0IsTM2zr0bwIAEzalkTa1UrlIRoA4wERVr811N1nq7blvqERqXjUY7PBB9OPH9lenCL8OwZhzzLHCyCsTwc4E0m7FPDobBeghLMkpISRnVOCNf_4P8vzm-R7kYUorQ3t1CsLmJzS3L3MTGrLHJtJf3fdyRbnPC_gA6DcAp</recordid><startdate>20110512</startdate><enddate>20110512</enddate><creator>Roescher, Nienke</creator><creator>Vosters, Jelle L</creator><creator>Yin, Hongen</creator><creator>Illei, Gabor G</creator><creator>Tak, Paul P</creator><creator>Chiorini, John A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110512</creationdate><title>Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent</title><author>Roescher, Nienke ; Vosters, Jelle L ; Yin, Hongen ; Illei, Gabor G ; Tak, Paul P ; Chiorini, John A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-3e73c12708479a75b77fe65abe108a883aec41e962f3d7f679b64d46234b32ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acids</topic><topic>Age</topic><topic>Animals</topic><topic>Antigens</topic><topic>Biology</topic><topic>Biopsy</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>Clinical trials</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Disease</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Glands</topic><topic>Immune system</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Intercellular adhesion molecule 1</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Leukocyte migration</topic><topic>LFA-1 antigen</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Multiple sclerosis</topic><topic>Patients</topic><topic>Physiology</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatology</topic><topic>Rodents</topic><topic>Saliva - secretion</topic><topic>Salivary glands</topic><topic>Sjogren's syndrome</topic><topic>Sjogren's Syndrome - immunology</topic><topic>Sjogren's Syndrome - metabolism</topic><topic>Tumor necrosis factor-TNF</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roescher, Nienke</creatorcontrib><creatorcontrib>Vosters, Jelle L</creatorcontrib><creatorcontrib>Yin, Hongen</creatorcontrib><creatorcontrib>Illei, Gabor G</creatorcontrib><creatorcontrib>Tak, Paul P</creatorcontrib><creatorcontrib>Chiorini, John A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roescher, Nienke</au><au>Vosters, Jelle L</au><au>Yin, Hongen</au><au>Illei, Gabor G</au><au>Tak, Paul P</au><au>Chiorini, John A</au><au>Shi, Songtao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-05-12</date><risdate>2011</risdate><volume>6</volume><issue>5</issue><spage>e19962</spage><epage>e19962</epage><pages>e19962-e19962</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.
A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).
Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA.
Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21589878</pmid><doi>10.1371/journal.pone.0019962</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-05, Vol.6 (5), p.e19962-e19962 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1294916432 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Age Animals Antigens Biology Biopsy CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell adhesion Cell adhesion & migration Cell migration Clinical trials Cytokines Dendritic cells Diabetes Diabetes mellitus Disease Female Gene therapy Glands Immune system Immunoglobulin A Immunoglobulin G Immunoglobulin M Immunoglobulins Immunology Inflammation Intercellular adhesion molecule 1 Intercellular Adhesion Molecule-1 - metabolism Leukocyte migration LFA-1 antigen Lymphocytes Lymphocytes B Lymphocytes T Medicine Mice Mice, Inbred NOD Multiple sclerosis Patients Physiology Rheumatoid arthritis Rheumatology Rodents Saliva - secretion Salivary glands Sjogren's syndrome Sjogren's Syndrome - immunology Sjogren's Syndrome - metabolism Tumor necrosis factor-TNF Viruses |
| title | Effect of soluble ICAM-1 on a Sjögren's syndrome-like phenotype in NOD mice is disease stage dependent |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T12%3A37%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20soluble%20ICAM-1%20on%20a%20Sj%C3%B6gren's%20syndrome-like%20phenotype%20in%20NOD%20mice%20is%20disease%20stage%20dependent&rft.jtitle=PloS%20one&rft.au=Roescher,%20Nienke&rft.date=2011-05-12&rft.volume=6&rft.issue=5&rft.spage=e19962&rft.epage=e19962&rft.pages=e19962-e19962&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0019962&rft_dat=%3Cproquest_plos_%3E2898626141%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1294916432&rft_id=info:pmid/21589878&rft_doaj_id=oai_doaj_org_article_e7e94273db88427781e2ce01653f7fed&rfr_iscdi=true |