Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells
Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic ti...
Gespeichert in:
| Veröffentlicht in: | Free radical biology & medicine 2005-12, Vol.39 (12), p.1560-1569 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1569 |
|---|---|
| container_issue | 12 |
| container_start_page | 1560 |
| container_title | Free radical biology & medicine |
| container_volume | 39 |
| creator | Linehan, John D. Kolios, George Valatas, Vassilis Robertson, Duncan A.F. Westwick, John |
| description | Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1. |
| doi_str_mv | 10.1016/j.freeradbiomed.2005.07.019 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68813097</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0891584905004442</els_id><sourcerecordid>68813097</sourcerecordid><originalsourceid>FETCH-LOGICAL-c412t-e2e7cdd5a4fde60288273f0807f063b649ae5720a374d8f273211279a069289e3</originalsourceid><addsrcrecordid>eNqNkU2r1TAQhoMo3uPVvyABwV3rJG3zgSu5XPXCBTe6Dmky1Rzbpiatetb-cVPOQXClEMhinndmmIeQFwxqBky8OtZDQkzW9yFO6GsO0NUga2D6ATkwJZuq7bR4SA6gNKs61eor8iTnIwC0XaMekysmuFZCsQP5dTdN2xyn6LfRrjGdqDut8WuYMdO8LUvCnCkuYf2CY7AjncOagqPxZ_BIl1Ribg1xpmF_w2in6dyljz9wpD5ktBlpf6K2cPNnWtApznHe3Ig2UYfjmJ-SR4MdMz67_Nfk09vbjzfvq_sP7-5u3txXrmV8rZCjdN53th08CuBKcdkMoEAOIJpetNpiJznYRrZeDaXIGeNSWxCaK43NNXl57lv2_rZhXs0U8r6BnTFu2QilWANa_hPk0CnWaV3A12fQpZhzwsEsKUw2nQwDs8syR_OXLLPLMiBNkVXSzy9jtn6v_cle7BTg9gxgucr3gMlkF3B26ENCtxofw38N-g1BvrDz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20581599</pqid></control><display><type>article</type><title>Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><source>MEDLINE</source><creator>Linehan, John D. ; Kolios, George ; Valatas, Vassilis ; Robertson, Duncan A.F. ; Westwick, John</creator><creatorcontrib>Linehan, John D. ; Kolios, George ; Valatas, Vassilis ; Robertson, Duncan A.F. ; Westwick, John</creatorcontrib><description>Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.</description><identifier>ISSN: 0891-5849</identifier><identifier>EISSN: 1873-4596</identifier><identifier>DOI: 10.1016/j.freeradbiomed.2005.07.019</identifier><identifier>PMID: 16298681</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Coculture Techniques ; Colitis, Ulcerative - immunology ; Colon - cytology ; Colon - drug effects ; Colon - metabolism ; Colonic epithelial cells ; Culture Media, Conditioned - pharmacology ; Cytokines - pharmacology ; Epithelial Cells - drug effects ; Epithelial Cells - immunology ; Female ; Free radicals ; HT29 Cells ; Humans ; Inflammatory bowel disease ; Inflammatory Bowel Diseases - genetics ; Inflammatory Bowel Diseases - immunology ; Inflammatory Bowel Diseases - physiopathology ; Interleukin 10 ; Interleukin-10 - pharmacology ; Interleukin-4 - pharmacology ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Male ; Middle Aged ; Nitric oxide ; Nitric Oxide - biosynthesis ; Nitric Oxide Synthase Type II - drug effects ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism</subject><ispartof>Free radical biology & medicine, 2005-12, Vol.39 (12), p.1560-1569</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-e2e7cdd5a4fde60288273f0807f063b649ae5720a374d8f273211279a069289e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.freeradbiomed.2005.07.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16298681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Linehan, John D.</creatorcontrib><creatorcontrib>Kolios, George</creatorcontrib><creatorcontrib>Valatas, Vassilis</creatorcontrib><creatorcontrib>Robertson, Duncan A.F.</creatorcontrib><creatorcontrib>Westwick, John</creatorcontrib><title>Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells</title><title>Free radical biology & medicine</title><addtitle>Free Radic Biol Med</addtitle><description>Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Coculture Techniques</subject><subject>Colitis, Ulcerative - immunology</subject><subject>Colon - cytology</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Colonic epithelial cells</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Cytokines - pharmacology</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - immunology</subject><subject>Female</subject><subject>Free radicals</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory Bowel Diseases - genetics</subject><subject>Inflammatory Bowel Diseases - immunology</subject><subject>Inflammatory Bowel Diseases - physiopathology</subject><subject>Interleukin 10</subject><subject>Interleukin-10 - pharmacology</subject><subject>Interleukin-4 - pharmacology</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide Synthase Type II - drug effects</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><issn>0891-5849</issn><issn>1873-4596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2r1TAQhoMo3uPVvyABwV3rJG3zgSu5XPXCBTe6Dmky1Rzbpiatetb-cVPOQXClEMhinndmmIeQFwxqBky8OtZDQkzW9yFO6GsO0NUga2D6ATkwJZuq7bR4SA6gNKs61eor8iTnIwC0XaMekysmuFZCsQP5dTdN2xyn6LfRrjGdqDut8WuYMdO8LUvCnCkuYf2CY7AjncOagqPxZ_BIl1Ribg1xpmF_w2in6dyljz9wpD5ktBlpf6K2cPNnWtApznHe3Ig2UYfjmJ-SR4MdMz67_Nfk09vbjzfvq_sP7-5u3txXrmV8rZCjdN53th08CuBKcdkMoEAOIJpetNpiJznYRrZeDaXIGeNSWxCaK43NNXl57lv2_rZhXs0U8r6BnTFu2QilWANa_hPk0CnWaV3A12fQpZhzwsEsKUw2nQwDs8syR_OXLLPLMiBNkVXSzy9jtn6v_cle7BTg9gxgucr3gMlkF3B26ENCtxofw38N-g1BvrDz</recordid><startdate>20051215</startdate><enddate>20051215</enddate><creator>Linehan, John D.</creator><creator>Kolios, George</creator><creator>Valatas, Vassilis</creator><creator>Robertson, Duncan A.F.</creator><creator>Westwick, John</creator><general>Elsevier Inc</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>20051215</creationdate><title>Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells</title><author>Linehan, John D. ; Kolios, George ; Valatas, Vassilis ; Robertson, Duncan A.F. ; Westwick, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-e2e7cdd5a4fde60288273f0807f063b649ae5720a374d8f273211279a069289e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Coculture Techniques</topic><topic>Colitis, Ulcerative - immunology</topic><topic>Colon - cytology</topic><topic>Colon - drug effects</topic><topic>Colon - metabolism</topic><topic>Colonic epithelial cells</topic><topic>Culture Media, Conditioned - pharmacology</topic><topic>Cytokines - pharmacology</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - immunology</topic><topic>Female</topic><topic>Free radicals</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory Bowel Diseases - genetics</topic><topic>Inflammatory Bowel Diseases - immunology</topic><topic>Inflammatory Bowel Diseases - physiopathology</topic><topic>Interleukin 10</topic><topic>Interleukin-10 - pharmacology</topic><topic>Interleukin-4 - pharmacology</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide Synthase Type II - drug effects</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Linehan, John D.</creatorcontrib><creatorcontrib>Kolios, George</creatorcontrib><creatorcontrib>Valatas, Vassilis</creatorcontrib><creatorcontrib>Robertson, Duncan A.F.</creatorcontrib><creatorcontrib>Westwick, John</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>Free radical biology & medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Linehan, John D.</au><au>Kolios, George</au><au>Valatas, Vassilis</au><au>Robertson, Duncan A.F.</au><au>Westwick, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells</atitle><jtitle>Free radical biology & medicine</jtitle><addtitle>Free Radic Biol Med</addtitle><date>2005-12-15</date><risdate>2005</risdate><volume>39</volume><issue>12</issue><spage>1560</spage><epage>1569</epage><pages>1560-1569</pages><issn>0891-5849</issn><eissn>1873-4596</eissn><abstract>Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16298681</pmid><doi>10.1016/j.freeradbiomed.2005.07.019</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0891-5849 |
| ispartof | Free radical biology & medicine, 2005-12, Vol.39 (12), p.1560-1569 |
| issn | 0891-5849 1873-4596 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68813097 |
| source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE |
| subjects | Adolescent Adult Aged Aged, 80 and over Coculture Techniques Colitis, Ulcerative - immunology Colon - cytology Colon - drug effects Colon - metabolism Colonic epithelial cells Culture Media, Conditioned - pharmacology Cytokines - pharmacology Epithelial Cells - drug effects Epithelial Cells - immunology Female Free radicals HT29 Cells Humans Inflammatory bowel disease Inflammatory Bowel Diseases - genetics Inflammatory Bowel Diseases - immunology Inflammatory Bowel Diseases - physiopathology Interleukin 10 Interleukin-10 - pharmacology Interleukin-4 - pharmacology Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Male Middle Aged Nitric oxide Nitric Oxide - biosynthesis Nitric Oxide Synthase Type II - drug effects Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism |
| title | Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T16%3A07%3A21IST&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=Immunomodulatory%20cytokines%20suppress%20epithelial%20nitric%20oxide%20production%20in%20inflammatory%20bowel%20disease%20by%20acting%20on%20mononuclear%20cells&rft.jtitle=Free%20radical%20biology%20&%20medicine&rft.au=Linehan,%20John%20D.&rft.date=2005-12-15&rft.volume=39&rft.issue=12&rft.spage=1560&rft.epage=1569&rft.pages=1560-1569&rft.issn=0891-5849&rft.eissn=1873-4596&rft_id=info:doi/10.1016/j.freeradbiomed.2005.07.019&rft_dat=%3Cproquest_cross%3E68813097%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=20581599&rft_id=info:pmid/16298681&rft_els_id=S0891584905004442&rfr_iscdi=true |