Interleukin-8/CXCl8 forms an autocrine loop in fetal intestinal mucosa
IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necr...
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| Veröffentlicht in: | Pediatric research 2004-08, Vol.56 (2), p.240-249 |
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| creator | MAHESHWARI, Akhil LACSON, Atilano WENGE LU FOX, Samuel E BARLEYCORN, Aaron A CHRISTENSEN, Robert D CALHOUN, Darlene A |
| description | IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-alpha and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-alpha. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism. |
| doi_str_mv | 10.1203/01.PDR.0000133196.25949.98 |
| format | Article |
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We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-alpha and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-alpha. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1203/01.PDR.0000133196.25949.98</identifier><identifier>PMID: 15181190</identifier><identifier>CODEN: PEREBL</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Autocrine Communication ; Biological and medical sciences ; Cell Death - physiology ; Cell Survival ; DNA Fragmentation ; Female ; Fetus - anatomy & histology ; Fetus - physiology ; Gastroenterology. Liver. Pancreas. Abdomen ; General aspects ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Interleukin-8 - genetics ; Interleukin-8 - metabolism ; Intestinal Mucosa - cytology ; Intestinal Mucosa - metabolism ; Medical sciences ; Other diseases. Semiology ; Pregnancy ; Receptors, Interleukin-8A - metabolism ; RNA, Messenger - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Pediatric research, 2004-08, Vol.56 (2), p.240-249</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-4aa1d1b8e0bc77737b6a9ff703220ffe8ad09f377faf1da135086cb20b2cfdc03</citedby><cites>FETCH-LOGICAL-c397t-4aa1d1b8e0bc77737b6a9ff703220ffe8ad09f377faf1da135086cb20b2cfdc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15975408$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15181190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MAHESHWARI, Akhil</creatorcontrib><creatorcontrib>LACSON, Atilano</creatorcontrib><creatorcontrib>WENGE LU</creatorcontrib><creatorcontrib>FOX, Samuel E</creatorcontrib><creatorcontrib>BARLEYCORN, Aaron A</creatorcontrib><creatorcontrib>CHRISTENSEN, Robert D</creatorcontrib><creatorcontrib>CALHOUN, Darlene A</creatorcontrib><title>Interleukin-8/CXCl8 forms an autocrine loop in fetal intestinal mucosa</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><description>IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-alpha and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-alpha. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism.</description><subject>Autocrine Communication</subject><subject>Biological and medical sciences</subject><subject>Cell Death - physiology</subject><subject>Cell Survival</subject><subject>DNA Fragmentation</subject><subject>Female</subject><subject>Fetus - anatomy & histology</subject><subject>Fetus - physiology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>General aspects</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Interleukin-8 - genetics</subject><subject>Interleukin-8 - metabolism</subject><subject>Intestinal Mucosa - cytology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Medical sciences</subject><subject>Other diseases. Semiology</subject><subject>Pregnancy</subject><subject>Receptors, Interleukin-8A - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1LxDAQhoMo7rr6F6QIemt3pmmbxJtUVxcWFFHwFtI0gWo_1qQ9-O-N7oLOZebwvDPDQ8gFQoIp0CVg8nT7nEAopBRFkaS5yEQi-AGZY04hhixjh2QOQDGmQvAZOfH-PeBZzrNjMsMcOaKAOVmt-9G41kwfTR_zZflWtjyyg-t8pPpITeOgXdObqB2GbdT0kTWjasMwGj82fRi7SQ9enZIjq1pvzvZ9QV5Xdy_lQ7x5vF-XN5tYU8HGOFMKa6y4gUozxiirCiWsZUDTFKw1XNUgLGXMKou1QpoDL3SVQpVqW2ugC3K127t1w-cUfpBd47VpW9WbYfKyKFgqUlEE8HoHajd474yVW9d0yn1JBPljUQLKYFH-WZS_FqXgIXy-vzJVnan_onttAbjcA8pr1Vqnet34f5xgeQacfgMeEXsT</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>MAHESHWARI, Akhil</creator><creator>LACSON, Atilano</creator><creator>WENGE LU</creator><creator>FOX, Samuel E</creator><creator>BARLEYCORN, Aaron A</creator><creator>CHRISTENSEN, Robert D</creator><creator>CALHOUN, Darlene A</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20040801</creationdate><title>Interleukin-8/CXCl8 forms an autocrine loop in fetal intestinal mucosa</title><author>MAHESHWARI, Akhil ; LACSON, Atilano ; WENGE LU ; FOX, Samuel E ; BARLEYCORN, Aaron A ; CHRISTENSEN, Robert D ; CALHOUN, Darlene A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-4aa1d1b8e0bc77737b6a9ff703220ffe8ad09f377faf1da135086cb20b2cfdc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Autocrine Communication</topic><topic>Biological and medical sciences</topic><topic>Cell Death - physiology</topic><topic>Cell Survival</topic><topic>DNA Fragmentation</topic><topic>Female</topic><topic>Fetus - anatomy & histology</topic><topic>Fetus - physiology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>General aspects</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Infant, Premature</topic><topic>Interleukin-8 - genetics</topic><topic>Interleukin-8 - metabolism</topic><topic>Intestinal Mucosa - cytology</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Medical sciences</topic><topic>Other diseases. Semiology</topic><topic>Pregnancy</topic><topic>Receptors, Interleukin-8A - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MAHESHWARI, Akhil</creatorcontrib><creatorcontrib>LACSON, Atilano</creatorcontrib><creatorcontrib>WENGE LU</creatorcontrib><creatorcontrib>FOX, Samuel E</creatorcontrib><creatorcontrib>BARLEYCORN, Aaron A</creatorcontrib><creatorcontrib>CHRISTENSEN, Robert D</creatorcontrib><creatorcontrib>CALHOUN, Darlene A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MAHESHWARI, Akhil</au><au>LACSON, Atilano</au><au>WENGE LU</au><au>FOX, Samuel E</au><au>BARLEYCORN, Aaron A</au><au>CHRISTENSEN, Robert D</au><au>CALHOUN, Darlene A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-8/CXCl8 forms an autocrine loop in fetal intestinal mucosa</atitle><jtitle>Pediatric research</jtitle><addtitle>Pediatr Res</addtitle><date>2004-08-01</date><risdate>2004</risdate><volume>56</volume><issue>2</issue><spage>240</spage><epage>249</epage><pages>240-249</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><coden>PEREBL</coden><abstract>IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-alpha and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-alpha. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15181190</pmid><doi>10.1203/01.PDR.0000133196.25949.98</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Pediatric research, 2004-08, Vol.56 (2), p.240-249 |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_66729296 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Autocrine Communication Biological and medical sciences Cell Death - physiology Cell Survival DNA Fragmentation Female Fetus - anatomy & histology Fetus - physiology Gastroenterology. Liver. Pancreas. Abdomen General aspects Gestational Age Humans Infant Infant, Newborn Infant, Premature Interleukin-8 - genetics Interleukin-8 - metabolism Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Medical sciences Other diseases. Semiology Pregnancy Receptors, Interleukin-8A - metabolism RNA, Messenger - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumor Necrosis Factor-alpha - metabolism |
| title | Interleukin-8/CXCl8 forms an autocrine loop in fetal intestinal mucosa |
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