Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium
In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneu...
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creator | Zahlten, Janine Herta, Toni Kabus, Christin Steinfeldt, Magdalena Kershaw, Olivia García, Pedro Hocke, Andreas C Gruber, Achim D Hübner, Ralf-Harto Steinicke, Robert Doehn, Jan-Moritz Suttorp, Norbert Hippenstiel, Stefan |
description | In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure. |
doi_str_mv | 10.1165/rcmb.2014-0024OC |
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In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure.</description><identifier>ISSN: 1044-1549</identifier><identifier>EISSN: 1535-4989</identifier><identifier>DOI: 10.1165/rcmb.2014-0024OC</identifier><identifier>PMID: 25756955</identifier><language>eng</language><publisher>United States: American Thoracic Society</publisher><subject>Bacterial Proteins - physiology ; Cell culture ; Cell Line ; Chemokines ; Deoxyribonucleic acid ; DNA ; Gene Expression Regulation - immunology ; Host-Pathogen Interactions ; Humans ; Immunoglobulins ; Infrared imaging systems ; Interleukin-8 - genetics ; Interleukin-8 - metabolism ; Interleukin-8 - secretion ; Kinases ; Kruppel-Like Transcription Factors - metabolism ; N-Acetylmuramoyl-L-alanine Amidase - physiology ; Plasmids ; Pneumonia ; Pneumonia, Pneumococcal - immunology ; Pneumonia, Pneumococcal - metabolism ; Pneumonia, Pneumococcal - microbiology ; Promoter Regions, Genetic ; Proteins ; Respiratory Mucosa - metabolism ; Respiratory Mucosa - microbiology ; Respiratory Mucosa - secretion ; Signal Transduction ; Streptococcus infections ; Streptococcus pneumoniae ; Streptococcus pneumoniae - enzymology ; Studies ; Toll-Like Receptor 9 - metabolism</subject><ispartof>American journal of respiratory cell and molecular biology, 2015-10, Vol.53 (4), p.544-554</ispartof><rights>Copyright American Thoracic Society Oct 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-4ce6cf796432ce5a48db9c7e95374c748a71a5e68a03b7e56a34e2e426e292123</citedby><cites>FETCH-LOGICAL-c407t-4ce6cf796432ce5a48db9c7e95374c748a71a5e68a03b7e56a34e2e426e292123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25756955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zahlten, Janine</creatorcontrib><creatorcontrib>Herta, Toni</creatorcontrib><creatorcontrib>Kabus, Christin</creatorcontrib><creatorcontrib>Steinfeldt, Magdalena</creatorcontrib><creatorcontrib>Kershaw, Olivia</creatorcontrib><creatorcontrib>García, Pedro</creatorcontrib><creatorcontrib>Hocke, Andreas C</creatorcontrib><creatorcontrib>Gruber, Achim D</creatorcontrib><creatorcontrib>Hübner, Ralf-Harto</creatorcontrib><creatorcontrib>Steinicke, Robert</creatorcontrib><creatorcontrib>Doehn, Jan-Moritz</creatorcontrib><creatorcontrib>Suttorp, Norbert</creatorcontrib><creatorcontrib>Hippenstiel, Stefan</creatorcontrib><title>Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure.</description><subject>Bacterial Proteins - physiology</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Chemokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene Expression Regulation - immunology</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Infrared imaging systems</subject><subject>Interleukin-8 - genetics</subject><subject>Interleukin-8 - metabolism</subject><subject>Interleukin-8 - secretion</subject><subject>Kinases</subject><subject>Kruppel-Like Transcription Factors - metabolism</subject><subject>N-Acetylmuramoyl-L-alanine Amidase - physiology</subject><subject>Plasmids</subject><subject>Pneumonia</subject><subject>Pneumonia, Pneumococcal - immunology</subject><subject>Pneumonia, Pneumococcal - metabolism</subject><subject>Pneumonia, Pneumococcal - microbiology</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Respiratory Mucosa - metabolism</subject><subject>Respiratory Mucosa - microbiology</subject><subject>Respiratory Mucosa - secretion</subject><subject>Signal Transduction</subject><subject>Streptococcus infections</subject><subject>Streptococcus pneumoniae</subject><subject>Streptococcus pneumoniae - enzymology</subject><subject>Studies</subject><subject>Toll-Like Receptor 9 - metabolism</subject><issn>1044-1549</issn><issn>1535-4989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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><recordid>eNqNkU1r3DAQhkVJaD7ae09BkEsuTjTySLKOYdltQha29ONYjFY7bry1ra1kQ_bf12aTHHLKaYbhmXcYHsa-gLgG0Oom-nZ9LQVgJoTE1ewDOwWVqwxtYY_GXiBmoNCesLOUtkKALAA-shOpjNJWqVP2-3toiIeKf-toaIMP3ruG3w59aPap7ngVIn9YLpDPn3aRUqpDx1234bNHasPfuiP-g3ykfpqP-HLo_vD5ru4fqamH9hM7rlyT6PNzPWe_FvOfs7tsufp6P7tdZh6F6TP0pH1lrMZcelIOi83aekNW5Qa9wcIZcIp04US-NqS0y5EkodQkrQSZn7OrQ-4uhn8Dpb5s6-SpaVxHYUglGGm0AQv4DhQKKxQWakQv36DbMMRufGQKBCOMVtNtcaB8DClFqspdrFsX9yWIcrJUTpbKyVJ5sDSuXDwHD-uWNq8LL1ry_1WtjGo</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Zahlten, Janine</creator><creator>Herta, Toni</creator><creator>Kabus, Christin</creator><creator>Steinfeldt, Magdalena</creator><creator>Kershaw, Olivia</creator><creator>García, Pedro</creator><creator>Hocke, Andreas C</creator><creator>Gruber, Achim D</creator><creator>Hübner, Ralf-Harto</creator><creator>Steinicke, Robert</creator><creator>Doehn, Jan-Moritz</creator><creator>Suttorp, Norbert</creator><creator>Hippenstiel, Stefan</creator><general>American Thoracic Society</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>7QL</scope><scope>C1K</scope></search><sort><creationdate>201510</creationdate><title>Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium</title><author>Zahlten, Janine ; Herta, Toni ; Kabus, Christin ; Steinfeldt, Magdalena ; Kershaw, Olivia ; García, Pedro ; Hocke, Andreas C ; Gruber, Achim D ; Hübner, Ralf-Harto ; Steinicke, Robert ; Doehn, Jan-Moritz ; Suttorp, Norbert ; Hippenstiel, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-4ce6cf796432ce5a48db9c7e95374c748a71a5e68a03b7e56a34e2e426e292123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Bacterial Proteins - 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Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zahlten, Janine</au><au>Herta, Toni</au><au>Kabus, Christin</au><au>Steinfeldt, Magdalena</au><au>Kershaw, Olivia</au><au>García, Pedro</au><au>Hocke, Andreas C</au><au>Gruber, Achim D</au><au>Hübner, Ralf-Harto</au><au>Steinicke, Robert</au><au>Doehn, Jan-Moritz</au><au>Suttorp, Norbert</au><au>Hippenstiel, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>2015-10</date><risdate>2015</risdate><volume>53</volume><issue>4</issue><spage>544</spage><epage>554</epage><pages>544-554</pages><issn>1044-1549</issn><eissn>1535-4989</eissn><abstract>In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure.</abstract><cop>United States</cop><pub>American Thoracic Society</pub><pmid>25756955</pmid><doi>10.1165/rcmb.2014-0024OC</doi><tpages>11</tpages></addata></record> |
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subjects | Bacterial Proteins - physiology Cell culture Cell Line Chemokines Deoxyribonucleic acid DNA Gene Expression Regulation - immunology Host-Pathogen Interactions Humans Immunoglobulins Infrared imaging systems Interleukin-8 - genetics Interleukin-8 - metabolism Interleukin-8 - secretion Kinases Kruppel-Like Transcription Factors - metabolism N-Acetylmuramoyl-L-alanine Amidase - physiology Plasmids Pneumonia Pneumonia, Pneumococcal - immunology Pneumonia, Pneumococcal - metabolism Pneumonia, Pneumococcal - microbiology Promoter Regions, Genetic Proteins Respiratory Mucosa - metabolism Respiratory Mucosa - microbiology Respiratory Mucosa - secretion Signal Transduction Streptococcus infections Streptococcus pneumoniae Streptococcus pneumoniae - enzymology Studies Toll-Like Receptor 9 - metabolism |
title | Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium |
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