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Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways
ABSTRACT Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasin...
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| Published in: | Respirology (Carlton, Vic.) Vic.), 2012-10, Vol.17 (7), p.1094-1100 |
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| creator | GRAINGE, CHRISTOPHER DULAY, VALDEEP WARD, JONATHAN SAMMUT, DAVID DAVIES, ELIZABETH GREEN, BENJAMIN LAU, LAURIE COTTEY, LAURA HAITCHI, HANS-MICHAEL DAVIES, DONNA E. HOWARTH, PETER H. |
| description | ABSTRACT
Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.
Methods: Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM‐β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM‐β mRNA.
Results: RELM‐β immunoreactivity, which co‐localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P |
| doi_str_mv | 10.1111/j.1440-1843.2012.02215.x |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1069206277</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1069206277</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4085-4c8374f3bb804a54e0424969a6cec31e1cf495f906a359769abb10a39ecc47903</originalsourceid><addsrcrecordid>eNqNkc9O3DAQhy3UCijtKyAfuST13zi-ICEKFERptbTiaDleB7w4MbUT7e5r8SB9pjos7Jm5zEjzzc_SZwAgRiXO9XVRYsZQgWtGS4IwKREhmJerHbC_XXzIMyW0EELKPfAppQVCiHLEd8EeIYLXhNB9cDezyaXB9YV3jxZ2wVszelv8e4YuQdfPR2PnsA3eh6Xr72ETQ28eggl9GqIzgws9DC3UaXjo9OAM1C4u9Tp9Bh9b7ZP98toPwJ_zs9-n34vrnxeXpyfXhWGo5gUzNRWspU1TI6Y5s4gRJiupK2MNxRablkneSlRpyqXIi6bBSFNpjWFCInoAjja5TzH8HW0aVOeSsd7r3oYxKYwqSVBFhMhovUFNDClF26qn6Dod1xlSk1a1UJM9NdlTk1b1olWt8unh6ytj09n59vDNYwaON8DSebt-d7Cand3-msYcUGwC8mfY1TZAx0dVCSq4uru5ULNv7PzHFUHqlv4H912Wug</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1069206277</pqid></control><display><type>article</type><title>Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways</title><source>Wiley</source><creator>GRAINGE, CHRISTOPHER ; DULAY, VALDEEP ; WARD, JONATHAN ; SAMMUT, DAVID ; DAVIES, ELIZABETH ; GREEN, BENJAMIN ; LAU, LAURIE ; COTTEY, LAURA ; HAITCHI, HANS-MICHAEL ; DAVIES, DONNA E. ; HOWARTH, PETER H.</creator><creatorcontrib>GRAINGE, CHRISTOPHER ; DULAY, VALDEEP ; WARD, JONATHAN ; SAMMUT, DAVID ; DAVIES, ELIZABETH ; GREEN, BENJAMIN ; LAU, LAURIE ; COTTEY, LAURA ; HAITCHI, HANS-MICHAEL ; DAVIES, DONNA E. ; HOWARTH, PETER H.</creatorcontrib><description>ABSTRACT
Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.
Methods: Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM‐β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM‐β mRNA.
Results: RELM‐β immunoreactivity, which co‐localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P < 0.001 between groups). RELM‐β immunoreactivity significantly and inversely correlated in asthma with forced expiratory volume in 1 s % predicted (P = 0.005). Acute changes in immunoexpression were evident after repeated inhalation challenge with allergen (2.15 % to 4.35 % (P = 0.01)) and methacholine (4.21 % to 6.16 % (P = 0.01)) but did not change in the salbutamol/methacholine challenge group. These changes correlated with change in basement membrane thickness (r = 0.38, P = 0.02). Epithelial RELM‐β gene expression was not altered in asthma.
Conclusions: RELM‐β may play an important role not only in animal models of airway remodelling, but also in human airway pathology.
Airway remodelling in asthma is associated with worse clinical outcomes but its cause is unknown. RELM‐β is necessary and sufficient to induce remodelling in mice. We demonstrate RELM‐β expression increasing with asthma severity, and further increasing following repeated bronchoconstriction, suggesting a potential role in human disease.</description><identifier>ISSN: 1323-7799</identifier><identifier>EISSN: 1440-1843</identifier><identifier>DOI: 10.1111/j.1440-1843.2012.02215.x</identifier><identifier>PMID: 22758223</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Adolescent ; Adult ; Aged ; Airway Remodeling - immunology ; allergen ; Allergens - immunology ; asthma ; Asthma - immunology ; Asthma - metabolism ; Bronchial Provocation Tests ; Bronchoconstriction - immunology ; Bronchoscopy ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - metabolism ; methacholine ; Methacholine Chloride ; Middle Aged ; remodelling ; resistin-like molecule-β ; Young Adult</subject><ispartof>Respirology (Carlton, Vic.), 2012-10, Vol.17 (7), p.1094-1100</ispartof><rights>2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology</rights><rights>2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4085-4c8374f3bb804a54e0424969a6cec31e1cf495f906a359769abb10a39ecc47903</citedby><cites>FETCH-LOGICAL-c4085-4c8374f3bb804a54e0424969a6cec31e1cf495f906a359769abb10a39ecc47903</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/22758223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GRAINGE, CHRISTOPHER</creatorcontrib><creatorcontrib>DULAY, VALDEEP</creatorcontrib><creatorcontrib>WARD, JONATHAN</creatorcontrib><creatorcontrib>SAMMUT, DAVID</creatorcontrib><creatorcontrib>DAVIES, ELIZABETH</creatorcontrib><creatorcontrib>GREEN, BENJAMIN</creatorcontrib><creatorcontrib>LAU, LAURIE</creatorcontrib><creatorcontrib>COTTEY, LAURA</creatorcontrib><creatorcontrib>HAITCHI, HANS-MICHAEL</creatorcontrib><creatorcontrib>DAVIES, DONNA E.</creatorcontrib><creatorcontrib>HOWARTH, PETER H.</creatorcontrib><title>Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways</title><title>Respirology (Carlton, Vic.)</title><addtitle>Respirology</addtitle><description>ABSTRACT
Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.
Methods: Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM‐β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM‐β mRNA.
Results: RELM‐β immunoreactivity, which co‐localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P < 0.001 between groups). RELM‐β immunoreactivity significantly and inversely correlated in asthma with forced expiratory volume in 1 s % predicted (P = 0.005). Acute changes in immunoexpression were evident after repeated inhalation challenge with allergen (2.15 % to 4.35 % (P = 0.01)) and methacholine (4.21 % to 6.16 % (P = 0.01)) but did not change in the salbutamol/methacholine challenge group. These changes correlated with change in basement membrane thickness (r = 0.38, P = 0.02). Epithelial RELM‐β gene expression was not altered in asthma.
Conclusions: RELM‐β may play an important role not only in animal models of airway remodelling, but also in human airway pathology.
Airway remodelling in asthma is associated with worse clinical outcomes but its cause is unknown. RELM‐β is necessary and sufficient to induce remodelling in mice. We demonstrate RELM‐β expression increasing with asthma severity, and further increasing following repeated bronchoconstriction, suggesting a potential role in human disease.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Airway Remodeling - immunology</subject><subject>allergen</subject><subject>Allergens - immunology</subject><subject>asthma</subject><subject>Asthma - immunology</subject><subject>Asthma - metabolism</subject><subject>Bronchial Provocation Tests</subject><subject>Bronchoconstriction - immunology</subject><subject>Bronchoscopy</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>methacholine</subject><subject>Methacholine Chloride</subject><subject>Middle Aged</subject><subject>remodelling</subject><subject>resistin-like molecule-β</subject><subject>Young Adult</subject><issn>1323-7799</issn><issn>1440-1843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkc9O3DAQhy3UCijtKyAfuST13zi-ICEKFERptbTiaDleB7w4MbUT7e5r8SB9pjos7Jm5zEjzzc_SZwAgRiXO9XVRYsZQgWtGS4IwKREhmJerHbC_XXzIMyW0EELKPfAppQVCiHLEd8EeIYLXhNB9cDezyaXB9YV3jxZ2wVszelv8e4YuQdfPR2PnsA3eh6Xr72ETQ28eggl9GqIzgws9DC3UaXjo9OAM1C4u9Tp9Bh9b7ZP98toPwJ_zs9-n34vrnxeXpyfXhWGo5gUzNRWspU1TI6Y5s4gRJiupK2MNxRablkneSlRpyqXIi6bBSFNpjWFCInoAjja5TzH8HW0aVOeSsd7r3oYxKYwqSVBFhMhovUFNDClF26qn6Dod1xlSk1a1UJM9NdlTk1b1olWt8unh6ytj09n59vDNYwaON8DSebt-d7Cand3-msYcUGwC8mfY1TZAx0dVCSq4uru5ULNv7PzHFUHqlv4H912Wug</recordid><startdate>201210</startdate><enddate>201210</enddate><creator>GRAINGE, CHRISTOPHER</creator><creator>DULAY, VALDEEP</creator><creator>WARD, JONATHAN</creator><creator>SAMMUT, DAVID</creator><creator>DAVIES, ELIZABETH</creator><creator>GREEN, BENJAMIN</creator><creator>LAU, LAURIE</creator><creator>COTTEY, LAURA</creator><creator>HAITCHI, HANS-MICHAEL</creator><creator>DAVIES, DONNA E.</creator><creator>HOWARTH, PETER H.</creator><general>Blackwell Publishing Asia</general><scope>BSCLL</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>201210</creationdate><title>Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways</title><author>GRAINGE, CHRISTOPHER ; DULAY, VALDEEP ; WARD, JONATHAN ; SAMMUT, DAVID ; DAVIES, ELIZABETH ; GREEN, BENJAMIN ; LAU, LAURIE ; COTTEY, LAURA ; HAITCHI, HANS-MICHAEL ; DAVIES, DONNA E. ; HOWARTH, PETER H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4085-4c8374f3bb804a54e0424969a6cec31e1cf495f906a359769abb10a39ecc47903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Airway Remodeling - immunology</topic><topic>allergen</topic><topic>Allergens - immunology</topic><topic>asthma</topic><topic>Asthma - immunology</topic><topic>Asthma - metabolism</topic><topic>Bronchial Provocation Tests</topic><topic>Bronchoconstriction - immunology</topic><topic>Bronchoscopy</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>methacholine</topic><topic>Methacholine Chloride</topic><topic>Middle Aged</topic><topic>remodelling</topic><topic>resistin-like molecule-β</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GRAINGE, CHRISTOPHER</creatorcontrib><creatorcontrib>DULAY, VALDEEP</creatorcontrib><creatorcontrib>WARD, JONATHAN</creatorcontrib><creatorcontrib>SAMMUT, DAVID</creatorcontrib><creatorcontrib>DAVIES, ELIZABETH</creatorcontrib><creatorcontrib>GREEN, BENJAMIN</creatorcontrib><creatorcontrib>LAU, LAURIE</creatorcontrib><creatorcontrib>COTTEY, LAURA</creatorcontrib><creatorcontrib>HAITCHI, HANS-MICHAEL</creatorcontrib><creatorcontrib>DAVIES, DONNA E.</creatorcontrib><creatorcontrib>HOWARTH, PETER H.</creatorcontrib><collection>Istex</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>Respirology (Carlton, Vic.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GRAINGE, CHRISTOPHER</au><au>DULAY, VALDEEP</au><au>WARD, JONATHAN</au><au>SAMMUT, DAVID</au><au>DAVIES, ELIZABETH</au><au>GREEN, BENJAMIN</au><au>LAU, LAURIE</au><au>COTTEY, LAURA</au><au>HAITCHI, HANS-MICHAEL</au><au>DAVIES, DONNA E.</au><au>HOWARTH, PETER H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways</atitle><jtitle>Respirology (Carlton, Vic.)</jtitle><addtitle>Respirology</addtitle><date>2012-10</date><risdate>2012</risdate><volume>17</volume><issue>7</issue><spage>1094</spage><epage>1100</epage><pages>1094-1100</pages><issn>1323-7799</issn><eissn>1440-1843</eissn><abstract>ABSTRACT
Background and objective: Resistin‐like molecule‐β (RELM‐β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM‐β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.
Methods: Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM‐β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM‐β mRNA.
Results: RELM‐β immunoreactivity, which co‐localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P < 0.001 between groups). RELM‐β immunoreactivity significantly and inversely correlated in asthma with forced expiratory volume in 1 s % predicted (P = 0.005). Acute changes in immunoexpression were evident after repeated inhalation challenge with allergen (2.15 % to 4.35 % (P = 0.01)) and methacholine (4.21 % to 6.16 % (P = 0.01)) but did not change in the salbutamol/methacholine challenge group. These changes correlated with change in basement membrane thickness (r = 0.38, P = 0.02). Epithelial RELM‐β gene expression was not altered in asthma.
Conclusions: RELM‐β may play an important role not only in animal models of airway remodelling, but also in human airway pathology.
Airway remodelling in asthma is associated with worse clinical outcomes but its cause is unknown. RELM‐β is necessary and sufficient to induce remodelling in mice. We demonstrate RELM‐β expression increasing with asthma severity, and further increasing following repeated bronchoconstriction, suggesting a potential role in human disease.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>22758223</pmid><doi>10.1111/j.1440-1843.2012.02215.x</doi><tpages>7</tpages></addata></record> |
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| source | Wiley |
| subjects | Adolescent Adult Aged Airway Remodeling - immunology allergen Allergens - immunology asthma Asthma - immunology Asthma - metabolism Bronchial Provocation Tests Bronchoconstriction - immunology Bronchoscopy Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins - metabolism methacholine Methacholine Chloride Middle Aged remodelling resistin-like molecule-β Young Adult |
| title | Resistin-like molecule-β is induced following bronchoconstriction of asthmatic airways |
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