Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase
Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N‐terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)‐...
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| Veröffentlicht in: | British journal of pharmacology 2003-12, Vol.140 (8), p.1373-1380 |
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| creator | Eynott, Paul R Nath, Puneeta Leung, Sum‐Yee Adcock, Ian M Bennett, Brydon L Chung, K Fan |
| description | Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N‐terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)‐1.
We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9‐cd] pyrazole‐6 (2 H)‐one), in a model of chronic allergic inflammation in the rat.
Rats sensitised to ovalbumin (OA) were exposed to OA‐aerosol every third day on six occasions and were treated with SP600125 (30 mg kg−1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T‐cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine.
SP600125 significantly reduced the number of eosinophils (P |
| doi_str_mv | 10.1038/sj.bjp.0705569 |
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We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9‐cd] pyrazole‐6 (2 H)‐one), in a model of chronic allergic inflammation in the rat.
Rats sensitised to ovalbumin (OA) were exposed to OA‐aerosol every third day on six occasions and were treated with SP600125 (30 mg kg−1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T‐cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine.
SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T‐cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05).
SP600125 did not alter bronchial hyper‐responsiveness observed after chronic allergen exposure.
Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.
British Journal of Pharmacology (2003) 140, 1373–1380. doi:10.1038/sj.bjp.0705569]]></description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0705569</identifier><identifier>PMID: 14623764</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Actins - metabolism ; airway inflammation ; Animals ; Anthracenes - pharmacology ; Asthma ; Biological and medical sciences ; Bronchi - drug effects ; Bronchi - immunology ; Bronchi - pathology ; bronchial hyper‐responsiveness ; Bronchoalveolar Lavage Fluid - chemistry ; Cell Count ; Cell Division - drug effects ; Chronic Disease ; c‐Jun‐N‐terminal kinase ; Eosinophils - drug effects ; Eosinophils - pathology ; epithelial cells ; Hypersensitivity - enzymology ; Hypersensitivity - immunology ; Hypersensitivity - pathology ; Immunohistochemistry ; Inflammation - enzymology ; Inflammation - immunology ; Inflammation - pathology ; JNK Mitogen-Activated Protein Kinases ; JNK protein ; Male ; Medical sciences ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - biosynthesis ; mitogen‐activated protein kinase ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - immunology ; Myocytes, Smooth Muscle - pathology ; Ovalbumin - immunology ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred BN ; Respiratory Mucosa - drug effects ; Respiratory Mucosa - immunology ; Respiratory Mucosa - metabolism ; signal transduction</subject><ispartof>British journal of pharmacology, 2003-12, Vol.140 (8), p.1373-1380</ispartof><rights>2003 British Pharmacological Society</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2003</rights><rights>Copyright 2003, Nature Publishing Group 2003 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5185-f012bd9f197fe2b4569ec8bf18c553d3af7eafe34d6189a41355b8e98812dd53</citedby><cites>FETCH-LOGICAL-c5185-f012bd9f197fe2b4569ec8bf18c553d3af7eafe34d6189a41355b8e98812dd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574155/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574155/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15366942$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14623764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eynott, Paul R</creatorcontrib><creatorcontrib>Nath, Puneeta</creatorcontrib><creatorcontrib>Leung, Sum‐Yee</creatorcontrib><creatorcontrib>Adcock, Ian M</creatorcontrib><creatorcontrib>Bennett, Brydon L</creatorcontrib><creatorcontrib>Chung, K Fan</creatorcontrib><title>Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description><![CDATA[Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N‐terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)‐1.
We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9‐cd] pyrazole‐6 (2 H)‐one), in a model of chronic allergic inflammation in the rat.
Rats sensitised to ovalbumin (OA) were exposed to OA‐aerosol every third day on six occasions and were treated with SP600125 (30 mg kg−1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T‐cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine.
SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T‐cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05).
SP600125 did not alter bronchial hyper‐responsiveness observed after chronic allergen exposure.
Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.
British Journal of Pharmacology (2003) 140, 1373–1380. doi:10.1038/sj.bjp.0705569]]></description><subject>Actins - metabolism</subject><subject>airway inflammation</subject><subject>Animals</subject><subject>Anthracenes - pharmacology</subject><subject>Asthma</subject><subject>Biological and medical sciences</subject><subject>Bronchi - drug effects</subject><subject>Bronchi - immunology</subject><subject>Bronchi - pathology</subject><subject>bronchial hyper‐responsiveness</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Cell Count</subject><subject>Cell Division - drug effects</subject><subject>Chronic Disease</subject><subject>c‐Jun‐N‐terminal kinase</subject><subject>Eosinophils - drug effects</subject><subject>Eosinophils - pathology</subject><subject>epithelial cells</subject><subject>Hypersensitivity - enzymology</subject><subject>Hypersensitivity - immunology</subject><subject>Hypersensitivity - pathology</subject><subject>Immunohistochemistry</subject><subject>Inflammation - enzymology</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>JNK protein</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - biosynthesis</subject><subject>mitogen‐activated protein kinase</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - immunology</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Ovalbumin - immunology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Respiratory Mucosa - drug effects</subject><subject>Respiratory Mucosa - immunology</subject><subject>Respiratory Mucosa - metabolism</subject><subject>signal transduction</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</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>eNqFkcFu1DAQhiMEokvhyhFZSHDLYsdx7HBAKhVQUAUcerccZ9x1cOytnVCtuPAIPCNPgrcbUeDCxZZnvvlnxn9RPCZ4TTAVL9Kw7obtGnPMWNPeKVak5k3JqCB3ixXGmJeECHFUPEhpwDgnObtfHJG6qShv6lXx7cQ5iJfgf37_YX0_a-iR9capcVSTDR4p3yNl47XaIdjaaQPOKncTTWMI0waNc9IOkAbn0DYGZw3Em9KXKL8ABYM-zB59zA0miKP1ufxLPhM8LO4Z5RI8Wu7j4uLtm4vTs_L807v3pyfnpWZEsNJgUnV9a0jLDVRdnfcELTpDhGaM9lQZDsoArfuGiFbVhDLWCWiFIFXfM3pcvDrIbuduhF6Dn6JychvtqOJOBmXl3xlvN_IyfJWE8ZqwvcDzRSCGqxnSJEeb9vsqD2FOkvAWV4yLDD79BxzCHPPCSVaEV_n_eZ2h9QHSMaQUwfyehGC591SmQWZP5eJpLnjy5_y3-GJiBp4tgEpaOROV1zbdcow2TVtXmaMH7to62P2nrXz9-axmFaO_AB18v_c</recordid><startdate>200312</startdate><enddate>200312</enddate><creator>Eynott, Paul R</creator><creator>Nath, Puneeta</creator><creator>Leung, Sum‐Yee</creator><creator>Adcock, Ian M</creator><creator>Bennett, Brydon L</creator><creator>Chung, K Fan</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>200312</creationdate><title>Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase</title><author>Eynott, Paul R ; Nath, Puneeta ; Leung, Sum‐Yee ; Adcock, Ian M ; Bennett, Brydon L ; Chung, K Fan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5185-f012bd9f197fe2b4569ec8bf18c553d3af7eafe34d6189a41355b8e98812dd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Actins - metabolism</topic><topic>airway inflammation</topic><topic>Animals</topic><topic>Anthracenes - pharmacology</topic><topic>Asthma</topic><topic>Biological and medical sciences</topic><topic>Bronchi - drug effects</topic><topic>Bronchi - immunology</topic><topic>Bronchi - pathology</topic><topic>bronchial hyper‐responsiveness</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Cell Count</topic><topic>Cell Division - drug effects</topic><topic>Chronic Disease</topic><topic>c‐Jun‐N‐terminal kinase</topic><topic>Eosinophils - drug effects</topic><topic>Eosinophils - pathology</topic><topic>epithelial cells</topic><topic>Hypersensitivity - enzymology</topic><topic>Hypersensitivity - immunology</topic><topic>Hypersensitivity - pathology</topic><topic>Immunohistochemistry</topic><topic>Inflammation - enzymology</topic><topic>Inflammation - immunology</topic><topic>Inflammation - pathology</topic><topic>JNK Mitogen-Activated Protein Kinases</topic><topic>JNK protein</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinases - biosynthesis</topic><topic>mitogen‐activated protein kinase</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - immunology</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Ovalbumin - immunology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Respiratory Mucosa - drug effects</topic><topic>Respiratory Mucosa - immunology</topic><topic>Respiratory Mucosa - metabolism</topic><topic>signal transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eynott, Paul R</creatorcontrib><creatorcontrib>Nath, Puneeta</creatorcontrib><creatorcontrib>Leung, Sum‐Yee</creatorcontrib><creatorcontrib>Adcock, Ian M</creatorcontrib><creatorcontrib>Bennett, Brydon L</creatorcontrib><creatorcontrib>Chung, K Fan</creatorcontrib><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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eynott, Paul R</au><au>Nath, Puneeta</au><au>Leung, Sum‐Yee</au><au>Adcock, Ian M</au><au>Bennett, Brydon L</au><au>Chung, K Fan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2003-12</date><risdate>2003</risdate><volume>140</volume><issue>8</issue><spage>1373</spage><epage>1380</epage><pages>1373-1380</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract><![CDATA[Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N‐terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)‐1.
We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9‐cd] pyrazole‐6 (2 H)‐one), in a model of chronic allergic inflammation in the rat.
Rats sensitised to ovalbumin (OA) were exposed to OA‐aerosol every third day on six occasions and were treated with SP600125 (30 mg kg−1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T‐cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine.
SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T‐cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05).
SP600125 did not alter bronchial hyper‐responsiveness observed after chronic allergen exposure.
Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.
British Journal of Pharmacology (2003) 140, 1373–1380. doi:10.1038/sj.bjp.0705569]]></abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>14623764</pmid><doi>10.1038/sj.bjp.0705569</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - metabolism airway inflammation Animals Anthracenes - pharmacology Asthma Biological and medical sciences Bronchi - drug effects Bronchi - immunology Bronchi - pathology bronchial hyper‐responsiveness Bronchoalveolar Lavage Fluid - chemistry Cell Count Cell Division - drug effects Chronic Disease c‐Jun‐N‐terminal kinase Eosinophils - drug effects Eosinophils - pathology epithelial cells Hypersensitivity - enzymology Hypersensitivity - immunology Hypersensitivity - pathology Immunohistochemistry Inflammation - enzymology Inflammation - immunology Inflammation - pathology JNK Mitogen-Activated Protein Kinases JNK protein Male Medical sciences Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - biosynthesis mitogen‐activated protein kinase Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - immunology Myocytes, Smooth Muscle - pathology Ovalbumin - immunology Pharmacology. Drug treatments Rats Rats, Inbred BN Respiratory Mucosa - drug effects Respiratory Mucosa - immunology Respiratory Mucosa - metabolism signal transduction |
| title | Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase |
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