Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells
Summary Background Acid‐sensing ion channels (ASIC) are a family of acid‐activated ligand‐gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR. Objectives The aim of the...
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Veröffentlicht in: | Clinical and experimental allergy 2012-07, Vol.42 (7), p.1028-1039 |
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creator | G. Khoo, S. Al-Alawi, M. Walsh, M. T. Hennigan, K. Glynn, S. Thornton, M. McQuaid, S. Wang, Y. Hamilton, P. W. Verriere, V. Gleich, G. J. Harvey, B. J. Costello, R. W. McGarvey, L. P. |
description | Summary
Background
Acid‐sensing ion channels (ASIC) are a family of acid‐activated ligand‐gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
Objectives
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
Methods
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
Results
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre‐treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC‐1 was equally expressed in both populations, but ASIC‐3 was significantly more highly expressed in AR (P |
doi_str_mv | 10.1111/j.1365-2222.2012.03980.x |
format | Article |
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Background
Acid‐sensing ion channels (ASIC) are a family of acid‐activated ligand‐gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
Objectives
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
Methods
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
Results
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre‐treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC‐1 was equally expressed in both populations, but ASIC‐3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC‐3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC‐3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC‐3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air‐surface liquid depth via an ASIC‐dependent chloride secretory pathway.
Conclusions
This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC‐3 expression.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2012.03980.x</identifier><identifier>PMID: 22702502</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>Acid Sensing Ion Channels ; acid-activated ligand-gated cation channels ; Acidity ; Acidosis ; Adolescent ; Adult ; Allergic rhinitis ; Amiloride ; Biological and medical sciences ; Biopsy ; cation channels ; Cells, Cultured ; Chloride ; Data processing ; eosinophil ; Eosinophil Peroxidase - metabolism ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelium ; Extracellular signal-regulated kinase ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Inflammation ; Lactic acid ; Lactic Acid - pharmacology ; Leukocytes (eosinophilic) ; Male ; MAP Kinase Signaling System ; Medical sciences ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Mucosa ; Nasal Mucosa - metabolism ; Nasal Mucosa - pathology ; Non tumoral diseases ; Nose ; Otorhinolaryngology. Stomatology ; Peroxidase ; pH effects ; Polymerase Chain Reaction ; Rhinitis, Allergic, Seasonal - metabolism ; Rhinitis, Allergic, Seasonal - pathology ; Sodium channels ; Sodium Channels - biosynthesis ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Clinical and experimental allergy, 2012-07, Vol.42 (7), p.1028-1039</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><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5640-ab42b7cc9c89f52fc8a601615724e94aaf9fc08b39b3e2f853ad93c628fb953d3</citedby><cites>FETCH-LOGICAL-c5640-ab42b7cc9c89f52fc8a601615724e94aaf9fc08b39b3e2f853ad93c628fb953d3</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.1365-2222.2012.03980.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2012.03980.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26016565$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22702502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>G. Khoo, S.</creatorcontrib><creatorcontrib>Al-Alawi, M.</creatorcontrib><creatorcontrib>Walsh, M. T.</creatorcontrib><creatorcontrib>Hennigan, K.</creatorcontrib><creatorcontrib>Glynn, S.</creatorcontrib><creatorcontrib>Thornton, M.</creatorcontrib><creatorcontrib>McQuaid, S.</creatorcontrib><creatorcontrib>Wang, Y.</creatorcontrib><creatorcontrib>Hamilton, P. W.</creatorcontrib><creatorcontrib>Verriere, V.</creatorcontrib><creatorcontrib>Gleich, G. J.</creatorcontrib><creatorcontrib>Harvey, B. J.</creatorcontrib><creatorcontrib>Costello, R. W.</creatorcontrib><creatorcontrib>McGarvey, L. P.</creatorcontrib><title>Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary
Background
Acid‐sensing ion channels (ASIC) are a family of acid‐activated ligand‐gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
Objectives
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
Methods
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
Results
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre‐treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC‐1 was equally expressed in both populations, but ASIC‐3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC‐3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC‐3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC‐3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air‐surface liquid depth via an ASIC‐dependent chloride secretory pathway.
Conclusions
This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC‐3 expression.</description><subject>Acid Sensing Ion Channels</subject><subject>acid-activated ligand-gated cation channels</subject><subject>Acidity</subject><subject>Acidosis</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Allergic rhinitis</subject><subject>Amiloride</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>cation channels</subject><subject>Cells, Cultured</subject><subject>Chloride</subject><subject>Data processing</subject><subject>eosinophil</subject><subject>Eosinophil Peroxidase - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelium</subject><subject>Extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Lactic acid</subject><subject>Lactic Acid - pharmacology</subject><subject>Leukocytes (eosinophilic)</subject><subject>Male</subject><subject>MAP Kinase Signaling System</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Mucosa</subject><subject>Nasal Mucosa - metabolism</subject><subject>Nasal Mucosa - pathology</subject><subject>Non tumoral diseases</subject><subject>Nose</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Peroxidase</subject><subject>pH effects</subject><subject>Polymerase Chain Reaction</subject><subject>Rhinitis, Allergic, Seasonal - metabolism</subject><subject>Rhinitis, Allergic, Seasonal - pathology</subject><subject>Sodium channels</subject><subject>Sodium Channels - biosynthesis</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUd1u0zAUthCIlcIrIEsIiZsUx46TGImLqeo2pKlc8LNLy3FOVhfXyexkdO_Cw2LTUiSudm5sH38_x_4QwjlZ5LHebxc5K3lGYy0oyemCMFGTxf4Jmp0unqIZEbzIqloUZ-hFCFtCCOOifo7OKK0I5YTO0K9VH4zrh42xeADf702rAmDj2klDwOMGMOwHDyGY3mHlWtxNTo_p0HdYadNmAVyUuMWppzfKObAZiwpYWQv-1mjsN8aZ0YQPqXtvRt9juDctOJ2csJ7sOHloMQwmGlqjLNZgbXiJnnXKBnh1XOfo28Xq6_Iqu_58-Wl5fp1pXhYkU01Bm0proWvRcdrpWpUkL3Ne0QJEoVQnOk3qhomGAe1qzlQrmC5p3TWCs5bN0buD7uD7uwnCKHcmpAmUg34KMie0KMtCCPoYaJ5TzqLJHL35D7rtJ-_iQ2TOqYjfT8okWB9Q2vcheOjk4M1O-YcoJVPYcitTpjJlKlPY8k_Ych-pr48GU7OD9kT8m24EvD0CVNDKdl45bcI_XPolXqZJPx5wP42Fh0cPIJer87SL_OzAN2GE_Ymv_A9ZVqzi8mZ9KS_Wy_XNl-9XUew38ujV4A</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>G. Khoo, S.</creator><creator>Al-Alawi, M.</creator><creator>Walsh, M. T.</creator><creator>Hennigan, K.</creator><creator>Glynn, S.</creator><creator>Thornton, M.</creator><creator>McQuaid, S.</creator><creator>Wang, Y.</creator><creator>Hamilton, P. W.</creator><creator>Verriere, V.</creator><creator>Gleich, G. J.</creator><creator>Harvey, B. J.</creator><creator>Costello, R. W.</creator><creator>McGarvey, L. P.</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></search><sort><creationdate>201207</creationdate><title>Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells</title><author>G. Khoo, S. ; Al-Alawi, M. ; Walsh, M. T. ; Hennigan, K. ; Glynn, S. ; Thornton, M. ; McQuaid, S. ; Wang, Y. ; Hamilton, P. W. ; Verriere, V. ; Gleich, G. J. ; Harvey, B. J. ; Costello, R. W. ; McGarvey, L. P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5640-ab42b7cc9c89f52fc8a601615724e94aaf9fc08b39b3e2f853ad93c628fb953d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acid Sensing Ion Channels</topic><topic>acid-activated ligand-gated cation channels</topic><topic>Acidity</topic><topic>Acidosis</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Allergic rhinitis</topic><topic>Amiloride</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>cation channels</topic><topic>Cells, Cultured</topic><topic>Chloride</topic><topic>Data processing</topic><topic>eosinophil</topic><topic>Eosinophil Peroxidase - metabolism</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelium</topic><topic>Extracellular signal-regulated kinase</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Lactic acid</topic><topic>Lactic Acid - pharmacology</topic><topic>Leukocytes (eosinophilic)</topic><topic>Male</topic><topic>MAP Kinase Signaling System</topic><topic>Medical sciences</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Mucosa</topic><topic>Nasal Mucosa - metabolism</topic><topic>Nasal Mucosa - pathology</topic><topic>Non tumoral diseases</topic><topic>Nose</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Peroxidase</topic><topic>pH effects</topic><topic>Polymerase Chain Reaction</topic><topic>Rhinitis, Allergic, Seasonal - metabolism</topic><topic>Rhinitis, Allergic, Seasonal - pathology</topic><topic>Sodium channels</topic><topic>Sodium Channels - biosynthesis</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>G. Khoo, S.</creatorcontrib><creatorcontrib>Al-Alawi, M.</creatorcontrib><creatorcontrib>Walsh, M. T.</creatorcontrib><creatorcontrib>Hennigan, K.</creatorcontrib><creatorcontrib>Glynn, S.</creatorcontrib><creatorcontrib>Thornton, M.</creatorcontrib><creatorcontrib>McQuaid, S.</creatorcontrib><creatorcontrib>Wang, Y.</creatorcontrib><creatorcontrib>Hamilton, P. W.</creatorcontrib><creatorcontrib>Verriere, V.</creatorcontrib><creatorcontrib>Gleich, G. J.</creatorcontrib><creatorcontrib>Harvey, B. J.</creatorcontrib><creatorcontrib>Costello, R. W.</creatorcontrib><creatorcontrib>McGarvey, L. P.</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><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>G. Khoo, S.</au><au>Al-Alawi, M.</au><au>Walsh, M. T.</au><au>Hennigan, K.</au><au>Glynn, S.</au><au>Thornton, M.</au><au>McQuaid, S.</au><au>Wang, Y.</au><au>Hamilton, P. W.</au><au>Verriere, V.</au><au>Gleich, G. J.</au><au>Harvey, B. J.</au><au>Costello, R. W.</au><au>McGarvey, L. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2012-07</date><risdate>2012</risdate><volume>42</volume><issue>7</issue><spage>1028</spage><epage>1039</epage><pages>1028-1039</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary
Background
Acid‐sensing ion channels (ASIC) are a family of acid‐activated ligand‐gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
Objectives
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
Methods
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
Results
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre‐treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC‐1 was equally expressed in both populations, but ASIC‐3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC‐3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC‐3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC‐3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air‐surface liquid depth via an ASIC‐dependent chloride secretory pathway.
Conclusions
This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC‐3 expression.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>22702502</pmid><doi>10.1111/j.1365-2222.2012.03980.x</doi><tpages>12</tpages></addata></record> |
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subjects | Acid Sensing Ion Channels acid-activated ligand-gated cation channels Acidity Acidosis Adolescent Adult Allergic rhinitis Amiloride Biological and medical sciences Biopsy cation channels Cells, Cultured Chloride Data processing eosinophil Eosinophil Peroxidase - metabolism Epithelial cells Epithelial Cells - metabolism Epithelial Cells - pathology Epithelium Extracellular signal-regulated kinase Female Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Regulation Humans Immunohistochemistry Inflammation Lactic acid Lactic Acid - pharmacology Leukocytes (eosinophilic) Male MAP Kinase Signaling System Medical sciences Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Mucosa Nasal Mucosa - metabolism Nasal Mucosa - pathology Non tumoral diseases Nose Otorhinolaryngology. Stomatology Peroxidase pH effects Polymerase Chain Reaction Rhinitis, Allergic, Seasonal - metabolism Rhinitis, Allergic, Seasonal - pathology Sodium channels Sodium Channels - biosynthesis Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
title | Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells |
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