Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation
Background The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF‐β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are r...
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| Veröffentlicht in: | International forum of allergy & rhinology 2015-07, Vol.5 (7), p.573-582 |
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| creator | Yamin, Moshe Holbrook, Eric H. Gray, Stacey T. Busaba, Nicolas Y. Lovett, Brooke Hamilos, Daniel L. |
| description | Background
The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF‐β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.
Methods
Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF‐β1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double‐stranded RNA (dsRNA) (a ligand for Toll‐like receptor‐3) and examined for inflammatory and profibrotic genes using real‐time polymerase chain reaction (PCR).
Results
CRSwNP patients showed increased TGF‐β1 and activin A in the stroma, increased TGF‐β1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3‐dependent Snail1 in the stroma. Immunostaining for TGF‐β1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF‐β1 and activin A and more strongly induced by dsRNA in terms of chemokines.
Conclusion
Increased TGF‐β1 and activin A and increased downstream TGF‐β1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF‐β1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling. |
| doi_str_mv | 10.1002/alr.21516 |
| format | Article |
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The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF‐β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.
Methods
Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF‐β1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double‐stranded RNA (dsRNA) (a ligand for Toll‐like receptor‐3) and examined for inflammatory and profibrotic genes using real‐time polymerase chain reaction (PCR).
Results
CRSwNP patients showed increased TGF‐β1 and activin A in the stroma, increased TGF‐β1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3‐dependent Snail1 in the stroma. Immunostaining for TGF‐β1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF‐β1 and activin A and more strongly induced by dsRNA in terms of chemokines.
Conclusion
Increased TGF‐β1 and activin A and increased downstream TGF‐β1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF‐β1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling.</description><identifier>ISSN: 2042-6976</identifier><identifier>EISSN: 2042-6984</identifier><identifier>DOI: 10.1002/alr.21516</identifier><identifier>PMID: 25914020</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Activin A ; Activins - metabolism ; Adult ; Aged ; airway remodeling ; Airway Remodeling - physiology ; Biopsy ; Chronic Disease ; chronic rhinosinusitis ; cigarette smoke ; epithelium ; Female ; Growth factors ; Humans ; inflammation ; Male ; Middle Aged ; Nasal Mucosa - drug effects ; Nasal Mucosa - metabolism ; nasal polyposis ; Nasal Polyps - metabolism ; Nasal Polyps - pathology ; Paranasal Sinuses - pathology ; profibrotic ; Real-Time Polymerase Chain Reaction ; Rhinitis - metabolism ; Rhinitis - pathology ; Sinusitis - metabolism ; Sinusitis - pathology ; Smoking - adverse effects ; TGF-β1 ; TLR 3 ; Toll-like receptor 3 ; Toll-Like Receptor 3 - metabolism ; transforming growth factor beta 1 ; Transforming Growth Factor beta1 - metabolism ; Turbinates - pathology ; Young Adult</subject><ispartof>International forum of allergy & rhinology, 2015-07, Vol.5 (7), p.573-582</ispartof><rights>2015 ARS‐AAOA, LLC</rights><rights>2015 ARS-AAOA, LLC.</rights><rights>2015 ARS-AAOA, LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4616-8778e3441c94420135355a903b2c1089bce6cdaf6040c17b0002ab70a3338673</citedby><cites>FETCH-LOGICAL-c4616-8778e3441c94420135355a903b2c1089bce6cdaf6040c17b0002ab70a3338673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falr.21516$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falr.21516$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25914020$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamin, Moshe</creatorcontrib><creatorcontrib>Holbrook, Eric H.</creatorcontrib><creatorcontrib>Gray, Stacey T.</creatorcontrib><creatorcontrib>Busaba, Nicolas Y.</creatorcontrib><creatorcontrib>Lovett, Brooke</creatorcontrib><creatorcontrib>Hamilos, Daniel L.</creatorcontrib><title>Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation</title><title>International forum of allergy & rhinology</title><addtitle>International Forum of Allergy and Rhinology</addtitle><description>Background
The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF‐β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.
Methods
Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF‐β1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double‐stranded RNA (dsRNA) (a ligand for Toll‐like receptor‐3) and examined for inflammatory and profibrotic genes using real‐time polymerase chain reaction (PCR).
Results
CRSwNP patients showed increased TGF‐β1 and activin A in the stroma, increased TGF‐β1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3‐dependent Snail1 in the stroma. Immunostaining for TGF‐β1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF‐β1 and activin A and more strongly induced by dsRNA in terms of chemokines.
Conclusion
Increased TGF‐β1 and activin A and increased downstream TGF‐β1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF‐β1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling.</description><subject>Activin A</subject><subject>Activins - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>airway remodeling</subject><subject>Airway Remodeling - physiology</subject><subject>Biopsy</subject><subject>Chronic Disease</subject><subject>chronic rhinosinusitis</subject><subject>cigarette smoke</subject><subject>epithelium</subject><subject>Female</subject><subject>Growth factors</subject><subject>Humans</subject><subject>inflammation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nasal Mucosa - drug effects</subject><subject>Nasal Mucosa - metabolism</subject><subject>nasal polyposis</subject><subject>Nasal Polyps - metabolism</subject><subject>Nasal Polyps - pathology</subject><subject>Paranasal Sinuses - pathology</subject><subject>profibrotic</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Rhinitis - metabolism</subject><subject>Rhinitis - pathology</subject><subject>Sinusitis - metabolism</subject><subject>Sinusitis - pathology</subject><subject>Smoking - adverse effects</subject><subject>TGF-β1</subject><subject>TLR 3</subject><subject>Toll-like receptor 3</subject><subject>Toll-Like Receptor 3 - metabolism</subject><subject>transforming growth factor beta 1</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Turbinates - pathology</subject><subject>Young Adult</subject><issn>2042-6976</issn><issn>2042-6984</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAUhaOqVUGUBS9QWeqmXQT8E-dnOUWFVpoWVI2ExMZynJvB4NjBdkrn1fp09RCYRVG98bX1nePre7LsiOBjgjE9kcYfU8JJ-Srbp7igednUxetdXZV72WEItzgtTjgn1dtsj_KGFJji_ezPpXe9br2LWqHopQ2984O2a7T27iHeoF6q6DxqIUpEkLQdShf6l7ZogaQHpK3yIAN0qUJWBmnQ6MxmRFGHMMGjQttuUi8JGHW8AaOnAbUbpPQ6-cUIKAzubhaunDG50enkQcG4bYQhk8ConX2XvemlCXD4tB9kq7Mvq9Ov-fLi_NvpYpmroiRlXldVDawoiGqKgmLCOONcNpi1VBFcN62CUnWyL3GBFanaNCcq2wpLxlhdVuwg-zjbjt7dTxCiGHRQYIy04KYgSJoxJemRJqEf_kFv3eRtam5L8aau6pom6tNMKe9C8NCL0etB-o0gWGwjFSlS8RhpYt8_OU7tAN2OfA4wAScz8KANbP7vJBbLn8-W-azQIcLvnUL6O5F-W3Fx9eNcXH6_Pvtcrmpxxf4CBXO60w</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Yamin, Moshe</creator><creator>Holbrook, Eric H.</creator><creator>Gray, Stacey T.</creator><creator>Busaba, Nicolas Y.</creator><creator>Lovett, Brooke</creator><creator>Hamilos, Daniel L.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201507</creationdate><title>Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation</title><author>Yamin, Moshe ; Holbrook, Eric H. ; Gray, Stacey T. ; Busaba, Nicolas Y. ; Lovett, Brooke ; Hamilos, Daniel L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4616-8778e3441c94420135355a903b2c1089bce6cdaf6040c17b0002ab70a3338673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Activin A</topic><topic>Activins - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>airway remodeling</topic><topic>Airway Remodeling - physiology</topic><topic>Biopsy</topic><topic>Chronic Disease</topic><topic>chronic rhinosinusitis</topic><topic>cigarette smoke</topic><topic>epithelium</topic><topic>Female</topic><topic>Growth factors</topic><topic>Humans</topic><topic>inflammation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nasal Mucosa - drug effects</topic><topic>Nasal Mucosa - metabolism</topic><topic>nasal polyposis</topic><topic>Nasal Polyps - metabolism</topic><topic>Nasal Polyps - pathology</topic><topic>Paranasal Sinuses - pathology</topic><topic>profibrotic</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Rhinitis - metabolism</topic><topic>Rhinitis - pathology</topic><topic>Sinusitis - metabolism</topic><topic>Sinusitis - pathology</topic><topic>Smoking - adverse effects</topic><topic>TGF-β1</topic><topic>TLR 3</topic><topic>Toll-like receptor 3</topic><topic>Toll-Like Receptor 3 - metabolism</topic><topic>transforming growth factor beta 1</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Turbinates - pathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamin, Moshe</creatorcontrib><creatorcontrib>Holbrook, Eric H.</creatorcontrib><creatorcontrib>Gray, Stacey T.</creatorcontrib><creatorcontrib>Busaba, Nicolas Y.</creatorcontrib><creatorcontrib>Lovett, Brooke</creatorcontrib><creatorcontrib>Hamilos, Daniel L.</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>International forum of allergy & rhinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamin, Moshe</au><au>Holbrook, Eric H.</au><au>Gray, Stacey T.</au><au>Busaba, Nicolas Y.</au><au>Lovett, Brooke</au><au>Hamilos, Daniel L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation</atitle><jtitle>International forum of allergy & rhinology</jtitle><addtitle>International Forum of Allergy and Rhinology</addtitle><date>2015-07</date><risdate>2015</risdate><volume>5</volume><issue>7</issue><spage>573</spage><epage>582</epage><pages>573-582</pages><issn>2042-6976</issn><eissn>2042-6984</eissn><abstract>Background
The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF‐β1) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.
Methods
Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF‐β1, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double‐stranded RNA (dsRNA) (a ligand for Toll‐like receptor‐3) and examined for inflammatory and profibrotic genes using real‐time polymerase chain reaction (PCR).
Results
CRSwNP patients showed increased TGF‐β1 and activin A in the stroma, increased TGF‐β1 signaling (phosphorylated Smad2/3) in the stroma and epithelium, and increased Smad3‐dependent Snail1 in the stroma. Immunostaining for TGF‐β1, pSmad2/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF‐β1 and activin A and more strongly induced by dsRNA in terms of chemokines.
Conclusion
Increased TGF‐β1 and activin A and increased downstream TGF‐β1 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF‐β1 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25914020</pmid><doi>10.1002/alr.21516</doi><tpages>10</tpages></addata></record> |
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| subjects | Activin A Activins - metabolism Adult Aged airway remodeling Airway Remodeling - physiology Biopsy Chronic Disease chronic rhinosinusitis cigarette smoke epithelium Female Growth factors Humans inflammation Male Middle Aged Nasal Mucosa - drug effects Nasal Mucosa - metabolism nasal polyposis Nasal Polyps - metabolism Nasal Polyps - pathology Paranasal Sinuses - pathology profibrotic Real-Time Polymerase Chain Reaction Rhinitis - metabolism Rhinitis - pathology Sinusitis - metabolism Sinusitis - pathology Smoking - adverse effects TGF-β1 TLR 3 Toll-like receptor 3 Toll-Like Receptor 3 - metabolism transforming growth factor beta 1 Transforming Growth Factor beta1 - metabolism Turbinates - pathology Young Adult |
| title | Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation |
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