Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma
Summary Background Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated. Objecti...
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| Veröffentlicht in: | Clinical and experimental allergy 2012-10, Vol.42 (10), p.1459-1471 |
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| creator | Ferreira, D. S. Annoni, R. Silva, L. F. F. Buttignol, M. Santos, A. B. G. Medeiros, M. C. R. Andrade, L. N. S. Yick, C. Y. Sterk, P. J. Sampaio, J. L. M. Dolhnikoff, M. Wenzel, S. E. Mauad, T. |
| description | Summary
Background
Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated.
Objective
To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non‐smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection.
Methods
Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non‐smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real‐time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects.
Results
Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non‐smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression.
Conclusions and Clinical Relevance
Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths. |
| doi_str_mv | 10.1111/j.1365-2222.2012.04047.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3459227</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3376399131</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6367-b709f61874844dc872939539ecab499cb8a86aef2d95dc055f0b471c2bd984603</originalsourceid><addsrcrecordid>eNqNkUuP0zAUhSMEYsrAX0CREBILEvx-LEAaVUNBjGAzCMTGchyHuuPEwU6h_fc401IeK-7CD93vHN2rUxQlBDXM9WJTQ8xohXLVCEBUAwIIr3d3isWpcbdYAElJxYUkZ8WDlDYAAEyluF-cISQlwQQvii_XwfvKuxtbRmvsOIWYSvS8xKUe2pLcntN63ztTpimGXvvS7_txHcbg7OSG0u7GaFNyYSjzr9NTJnSa1r1-WNzrtE_20fE-Lz6-vrxevqmuPqzeLi-uKsMw41XDgewYFJwIQlojOJJYUiyt0Q2R0jRCC6Zth1pJWwMo7UBDODSoaaUgDODz4tXBd9w2vW2NHaaovRqj63Xcq6Cd-rszuLX6Gr4rTKhEiGeDZ0eDGL5tbZpU75Kx3uvBhm1SEDCJIBCMZPTJP-gmbOOQ11OQEsolkmQ2FAfKxJBStN1pGAjUHKDaqDknNeek5gDVbYBql6WP_1zmJPyVWAaeHgGdjPZd1INx6TfHCCRQssy9PHA_nLf7_x5ALS8v5lfWVwe9S5PdnfQ63ijGMafq0_uVQvwzW8J3WK3wT3v9xLg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1545792947</pqid></control><display><type>article</type><title>Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Ferreira, D. S. ; Annoni, R. ; Silva, L. F. F. ; Buttignol, M. ; Santos, A. B. G. ; Medeiros, M. C. R. ; Andrade, L. N. S. ; Yick, C. Y. ; Sterk, P. J. ; Sampaio, J. L. M. ; Dolhnikoff, M. ; Wenzel, S. E. ; Mauad, T.</creator><creatorcontrib>Ferreira, D. S. ; Annoni, R. ; Silva, L. F. F. ; Buttignol, M. ; Santos, A. B. G. ; Medeiros, M. C. R. ; Andrade, L. N. S. ; Yick, C. Y. ; Sterk, P. J. ; Sampaio, J. L. M. ; Dolhnikoff, M. ; Wenzel, S. E. ; Mauad, T.</creatorcontrib><description>Summary
Background
Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated.
Objective
To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non‐smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection.
Methods
Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non‐smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real‐time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects.
Results
Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non‐smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression.
Conclusions and Clinical Relevance
Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.</description><identifier>ISSN: 0954-7894</identifier><identifier>ISSN: 1365-2222</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2012.04047.x</identifier><identifier>PMID: 22994343</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>Adult ; Asthma ; Asthma - immunology ; Asthma - mortality ; Biological and medical sciences ; Chronic obstructive pulmonary disease, asthma ; Cytokines - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; immunohistochemistry ; Inflammation - immunology ; innate immunity ; lung ; Lung - immunology ; Male ; Medical research ; Medical sciences ; Middle Aged ; Pneumology ; Thymic Stromal Lymphopoietin ; Toll-Like Receptor 2 - metabolism ; Toll-Like Receptor 3 - metabolism ; Toll-Like Receptor 4 - metabolism ; Up-Regulation</subject><ispartof>Clinical and experimental allergy, 2012-10, Vol.42 (10), p.1459-1471</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><rights>2012 Blackwell Publishing Ltd.</rights><rights>Copyright © 2012 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6367-b709f61874844dc872939539ecab499cb8a86aef2d95dc055f0b471c2bd984603</citedby><cites>FETCH-LOGICAL-c6367-b709f61874844dc872939539ecab499cb8a86aef2d95dc055f0b471c2bd984603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2222.2012.04047.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2012.04047.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26414196$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22994343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferreira, D. S.</creatorcontrib><creatorcontrib>Annoni, R.</creatorcontrib><creatorcontrib>Silva, L. F. F.</creatorcontrib><creatorcontrib>Buttignol, M.</creatorcontrib><creatorcontrib>Santos, A. B. G.</creatorcontrib><creatorcontrib>Medeiros, M. C. R.</creatorcontrib><creatorcontrib>Andrade, L. N. S.</creatorcontrib><creatorcontrib>Yick, C. Y.</creatorcontrib><creatorcontrib>Sterk, P. J.</creatorcontrib><creatorcontrib>Sampaio, J. L. M.</creatorcontrib><creatorcontrib>Dolhnikoff, M.</creatorcontrib><creatorcontrib>Wenzel, S. E.</creatorcontrib><creatorcontrib>Mauad, T.</creatorcontrib><title>Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary
Background
Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated.
Objective
To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non‐smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection.
Methods
Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non‐smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real‐time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects.
Results
Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non‐smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression.
Conclusions and Clinical Relevance
Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.</description><subject>Adult</subject><subject>Asthma</subject><subject>Asthma - immunology</subject><subject>Asthma - mortality</subject><subject>Biological and medical sciences</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>immunohistochemistry</subject><subject>Inflammation - immunology</subject><subject>innate immunity</subject><subject>lung</subject><subject>Lung - immunology</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pneumology</subject><subject>Thymic Stromal Lymphopoietin</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Toll-Like Receptor 3 - metabolism</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Up-Regulation</subject><issn>0954-7894</issn><issn>1365-2222</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUuP0zAUhSMEYsrAX0CREBILEvx-LEAaVUNBjGAzCMTGchyHuuPEwU6h_fc401IeK-7CD93vHN2rUxQlBDXM9WJTQ8xohXLVCEBUAwIIr3d3isWpcbdYAElJxYUkZ8WDlDYAAEyluF-cISQlwQQvii_XwfvKuxtbRmvsOIWYSvS8xKUe2pLcntN63ztTpimGXvvS7_txHcbg7OSG0u7GaFNyYSjzr9NTJnSa1r1-WNzrtE_20fE-Lz6-vrxevqmuPqzeLi-uKsMw41XDgewYFJwIQlojOJJYUiyt0Q2R0jRCC6Zth1pJWwMo7UBDODSoaaUgDODz4tXBd9w2vW2NHaaovRqj63Xcq6Cd-rszuLX6Gr4rTKhEiGeDZ0eDGL5tbZpU75Kx3uvBhm1SEDCJIBCMZPTJP-gmbOOQ11OQEsolkmQ2FAfKxJBStN1pGAjUHKDaqDknNeek5gDVbYBql6WP_1zmJPyVWAaeHgGdjPZd1INx6TfHCCRQssy9PHA_nLf7_x5ALS8v5lfWVwe9S5PdnfQ63ijGMafq0_uVQvwzW8J3WK3wT3v9xLg</recordid><startdate>201210</startdate><enddate>201210</enddate><creator>Ferreira, D. S.</creator><creator>Annoni, R.</creator><creator>Silva, L. F. F.</creator><creator>Buttignol, M.</creator><creator>Santos, A. B. G.</creator><creator>Medeiros, M. C. R.</creator><creator>Andrade, L. N. S.</creator><creator>Yick, C. Y.</creator><creator>Sterk, P. J.</creator><creator>Sampaio, J. L. M.</creator><creator>Dolhnikoff, M.</creator><creator>Wenzel, S. E.</creator><creator>Mauad, T.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201210</creationdate><title>Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma</title><author>Ferreira, D. S. ; Annoni, R. ; Silva, L. F. F. ; Buttignol, M. ; Santos, A. B. G. ; Medeiros, M. C. R. ; Andrade, L. N. S. ; Yick, C. Y. ; Sterk, P. J. ; Sampaio, J. L. M. ; Dolhnikoff, M. ; Wenzel, S. E. ; Mauad, T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6367-b709f61874844dc872939539ecab499cb8a86aef2d95dc055f0b471c2bd984603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Asthma</topic><topic>Asthma - immunology</topic><topic>Asthma - mortality</topic><topic>Biological and medical sciences</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Cytokines - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>immunohistochemistry</topic><topic>Inflammation - immunology</topic><topic>innate immunity</topic><topic>lung</topic><topic>Lung - immunology</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pneumology</topic><topic>Thymic Stromal Lymphopoietin</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Toll-Like Receptor 3 - metabolism</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferreira, D. S.</creatorcontrib><creatorcontrib>Annoni, R.</creatorcontrib><creatorcontrib>Silva, L. F. F.</creatorcontrib><creatorcontrib>Buttignol, M.</creatorcontrib><creatorcontrib>Santos, A. B. G.</creatorcontrib><creatorcontrib>Medeiros, M. C. R.</creatorcontrib><creatorcontrib>Andrade, L. N. S.</creatorcontrib><creatorcontrib>Yick, C. Y.</creatorcontrib><creatorcontrib>Sterk, P. J.</creatorcontrib><creatorcontrib>Sampaio, J. L. M.</creatorcontrib><creatorcontrib>Dolhnikoff, M.</creatorcontrib><creatorcontrib>Wenzel, S. E.</creatorcontrib><creatorcontrib>Mauad, T.</creatorcontrib><collection>Istex</collection><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferreira, D. S.</au><au>Annoni, R.</au><au>Silva, L. F. F.</au><au>Buttignol, M.</au><au>Santos, A. B. G.</au><au>Medeiros, M. C. R.</au><au>Andrade, L. N. S.</au><au>Yick, C. Y.</au><au>Sterk, P. J.</au><au>Sampaio, J. L. M.</au><au>Dolhnikoff, M.</au><au>Wenzel, S. E.</au><au>Mauad, T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2012-10</date><risdate>2012</risdate><volume>42</volume><issue>10</issue><spage>1459</spage><epage>1471</epage><pages>1459-1471</pages><issn>0954-7894</issn><issn>1365-2222</issn><eissn>1365-2222</eissn><abstract>Summary
Background
Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated.
Objective
To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non‐smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection.
Methods
Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non‐smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real‐time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects.
Results
Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non‐smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression.
Conclusions and Clinical Relevance
Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>22994343</pmid><doi>10.1111/j.1365-2222.2012.04047.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0954-7894 |
| ispartof | Clinical and experimental allergy, 2012-10, Vol.42 (10), p.1459-1471 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Asthma Asthma - immunology Asthma - mortality Biological and medical sciences Chronic obstructive pulmonary disease, asthma Cytokines - metabolism Female Fundamental and applied biological sciences. Psychology Fundamental immunology Humans immunohistochemistry Inflammation - immunology innate immunity lung Lung - immunology Male Medical research Medical sciences Middle Aged Pneumology Thymic Stromal Lymphopoietin Toll-Like Receptor 2 - metabolism Toll-Like Receptor 3 - metabolism Toll-Like Receptor 4 - metabolism Up-Regulation |
| title | Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma |
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