IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice
Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 1999-08, Vol.163 (3), p.1529-1536 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1536 |
|---|---|
| container_issue | 3 |
| container_start_page | 1529 |
| container_title | The Journal of immunology (1950) |
| container_volume | 163 |
| creator | Salkowski, Cindy A Kopydlowski, Karen Blanco, Jorge Cody, M. Joshua McNally, Ranney Vogel, Stefanie N |
| description | Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production. |
| doi_str_mv | 10.4049/jimmunol.163.3.1529 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69907252</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69907252</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-9325dc80e0216fd492394a4e09af5f2050414dd7e6d28fe5c271f049d0792d03</originalsourceid><addsrcrecordid>eNqFkE1PAjEQhhujEUR_gYnpSU-7Tj-XHg0KEiEmhntTt11Y3A_csiH8e4uLCTdPM4fnfTPzIHRLIObA1eM6L8u2qouYSBazmAiqzlCfCAGRlCDPUR-A0ogkMumhK-_XACCB8kvUI8CJACH7aDKdRYTiqcfPe9-4ZVuYrbM4r_DcpE29WZml8zhr6hJPP8YRwaayvxvFb1WdftXtFs_z1F2ji8wU3t0c5wAtxi-L0Ws0e59MR0-zKOWgtpFiVNh0CA4okZnlijLFDXegTCYyCiIcxq1NnLR0mDmR0oRk4VkLiaIW2ADdd7Wbpv5und_qMvepKwpTubr1WioFCRX0X5AkjMJQsQCyDgzf-mAg05smL02z1wT0wbP-86yDZ830wXNI3R3r28_S2ZNMJzYADx2wyperXd447UtTFAEnerfbnVT9ALTNhPA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17320893</pqid></control><display><type>article</type><title>IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Salkowski, Cindy A ; Kopydlowski, Karen ; Blanco, Jorge ; Cody, M. Joshua ; McNally, Ranney ; Vogel, Stefanie N</creator><creatorcontrib>Salkowski, Cindy A ; Kopydlowski, Karen ; Blanco, Jorge ; Cody, M. Joshua ; McNally, Ranney ; Vogel, Stefanie N</creatorcontrib><description>Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.163.3.1529</identifier><identifier>PMID: 10415056</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Consensus Sequence ; DNA-Binding Proteins - genetics ; Interferon Regulatory Factor-1 ; Interferon Regulatory Factor-2 ; Interferon Regulatory Factors ; Interferon-gamma - biosynthesis ; Interferon-gamma - immunology ; Interferon-gamma - pharmacology ; Interleukin-12 - biosynthesis ; Interleukin-12 - genetics ; Interleukin-12 - physiology ; Interleukin-12 - secretion ; Lipopolysaccharides - pharmacology ; Macrophages, Peritoneal - immunology ; Macrophages, Peritoneal - metabolism ; Macrophages, Peritoneal - microbiology ; Macrophages, Peritoneal - secretion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphoproteins - genetics ; Repressor Proteins - biosynthesis ; RNA, Messenger - biosynthesis ; Staphylococcus aureus - immunology ; Transcription Factors ; Up-Regulation - immunology ; Zymosan - immunology</subject><ispartof>The Journal of immunology (1950), 1999-08, Vol.163 (3), p.1529-1536</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-9325dc80e0216fd492394a4e09af5f2050414dd7e6d28fe5c271f049d0792d03</citedby><cites>FETCH-LOGICAL-c409t-9325dc80e0216fd492394a4e09af5f2050414dd7e6d28fe5c271f049d0792d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10415056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salkowski, Cindy A</creatorcontrib><creatorcontrib>Kopydlowski, Karen</creatorcontrib><creatorcontrib>Blanco, Jorge</creatorcontrib><creatorcontrib>Cody, M. Joshua</creatorcontrib><creatorcontrib>McNally, Ranney</creatorcontrib><creatorcontrib>Vogel, Stefanie N</creatorcontrib><title>IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production.</description><subject>Animals</subject><subject>Consensus Sequence</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Interferon Regulatory Factor-1</subject><subject>Interferon Regulatory Factor-2</subject><subject>Interferon Regulatory Factors</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-12 - physiology</subject><subject>Interleukin-12 - secretion</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophages, Peritoneal - immunology</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Macrophages, Peritoneal - microbiology</subject><subject>Macrophages, Peritoneal - secretion</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phosphoproteins - genetics</subject><subject>Repressor Proteins - biosynthesis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Staphylococcus aureus - immunology</subject><subject>Transcription Factors</subject><subject>Up-Regulation - immunology</subject><subject>Zymosan - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PAjEQhhujEUR_gYnpSU-7Tj-XHg0KEiEmhntTt11Y3A_csiH8e4uLCTdPM4fnfTPzIHRLIObA1eM6L8u2qouYSBazmAiqzlCfCAGRlCDPUR-A0ogkMumhK-_XACCB8kvUI8CJACH7aDKdRYTiqcfPe9-4ZVuYrbM4r_DcpE29WZml8zhr6hJPP8YRwaayvxvFb1WdftXtFs_z1F2ji8wU3t0c5wAtxi-L0Ws0e59MR0-zKOWgtpFiVNh0CA4okZnlijLFDXegTCYyCiIcxq1NnLR0mDmR0oRk4VkLiaIW2ADdd7Wbpv5und_qMvepKwpTubr1WioFCRX0X5AkjMJQsQCyDgzf-mAg05smL02z1wT0wbP-86yDZ830wXNI3R3r28_S2ZNMJzYADx2wyperXd447UtTFAEnerfbnVT9ALTNhPA</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Salkowski, Cindy A</creator><creator>Kopydlowski, Karen</creator><creator>Blanco, Jorge</creator><creator>Cody, M. Joshua</creator><creator>McNally, Ranney</creator><creator>Vogel, Stefanie N</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>7X8</scope></search><sort><creationdate>19990801</creationdate><title>IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice</title><author>Salkowski, Cindy A ; Kopydlowski, Karen ; Blanco, Jorge ; Cody, M. Joshua ; McNally, Ranney ; Vogel, Stefanie N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-9325dc80e0216fd492394a4e09af5f2050414dd7e6d28fe5c271f049d0792d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Consensus Sequence</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Interferon Regulatory Factor-1</topic><topic>Interferon Regulatory Factor-2</topic><topic>Interferon Regulatory Factors</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interferon-gamma - immunology</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin-12 - biosynthesis</topic><topic>Interleukin-12 - genetics</topic><topic>Interleukin-12 - physiology</topic><topic>Interleukin-12 - secretion</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophages, Peritoneal - immunology</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Macrophages, Peritoneal - microbiology</topic><topic>Macrophages, Peritoneal - secretion</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Phosphoproteins - genetics</topic><topic>Repressor Proteins - biosynthesis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Staphylococcus aureus - immunology</topic><topic>Transcription Factors</topic><topic>Up-Regulation - immunology</topic><topic>Zymosan - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salkowski, Cindy A</creatorcontrib><creatorcontrib>Kopydlowski, Karen</creatorcontrib><creatorcontrib>Blanco, Jorge</creatorcontrib><creatorcontrib>Cody, M. Joshua</creatorcontrib><creatorcontrib>McNally, Ranney</creatorcontrib><creatorcontrib>Vogel, Stefanie N</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>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salkowski, Cindy A</au><au>Kopydlowski, Karen</au><au>Blanco, Jorge</au><au>Cody, M. Joshua</au><au>McNally, Ranney</au><au>Vogel, Stefanie N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>163</volume><issue>3</issue><spage>1529</spage><epage>1536</epage><pages>1529-1536</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>10415056</pmid><doi>10.4049/jimmunol.163.3.1529</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 1999-08, Vol.163 (3), p.1529-1536 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69907252 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Consensus Sequence DNA-Binding Proteins - genetics Interferon Regulatory Factor-1 Interferon Regulatory Factor-2 Interferon Regulatory Factors Interferon-gamma - biosynthesis Interferon-gamma - immunology Interferon-gamma - pharmacology Interleukin-12 - biosynthesis Interleukin-12 - genetics Interleukin-12 - physiology Interleukin-12 - secretion Lipopolysaccharides - pharmacology Macrophages, Peritoneal - immunology Macrophages, Peritoneal - metabolism Macrophages, Peritoneal - microbiology Macrophages, Peritoneal - secretion Mice Mice, Inbred C57BL Mice, Knockout Phosphoproteins - genetics Repressor Proteins - biosynthesis RNA, Messenger - biosynthesis Staphylococcus aureus - immunology Transcription Factors Up-Regulation - immunology Zymosan - immunology |
| title | IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A44%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=IL-12%20Is%20Dysregulated%20in%20Macrophages%20from%20IRF-1%20and%20IRF-2%20Knockout%20Mice&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Salkowski,%20Cindy%20A&rft.date=1999-08-01&rft.volume=163&rft.issue=3&rft.spage=1529&rft.epage=1536&rft.pages=1529-1536&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.163.3.1529&rft_dat=%3Cproquest_cross%3E69907252%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17320893&rft_id=info:pmid/10415056&rfr_iscdi=true |