Transforming growth factor-β1 and cigarette smoke inhibit the ability of β2-agonists to enhance epithelial permeability
Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradi...
Saved in:
Published in | American journal of respiratory cell and molecular biology Vol. 52; no. 1; pp. 65 - 74 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Thoracic Society
01.01.2015
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradient for serosal to mucosal fluid transport through its ability to both secrete Cl(-) and regulate paracellular permeability, but CFTR activity is attenuated in chronic bronchitis and in smokers. β2-adrenergic receptor (β2-AR) agonists are widely used for managing chronic obstructive pulmonary disease, and can activate CFTR, stimulate ciliary beat frequency, and increase epithelial permeability, thereby stimulating MCC. Patients with chronic airway diseases and cigarette smokers demonstrate increased transforming growth factor (TGF)-β1 signaling, which suppresses β2-agonist-mediated CFTR activation and epithelial permeability increases. Restoring CFTR function in these diseases can restore the ability of β2-agonists to enhance epithelial permeability. Human bronchial epithelial cells, fully redifferentiated at the air-liquid interface, were used for (14)C mannitol flux measurements, Ussing chamber experiments, and quantitative RT-PCR. β2-agonists enhance epithelial permeability by activating CFTR via the β2-AR/adenylyl cyclase/cAMP/protein kinase A pathway. TGF-β1 inhibits β2-agonist-mediated CFTR activation and epithelial permeability enhancement. Although TGF-β1 down-regulates both β2-AR and CFTR mRNA, functionally it only decreases CFTR activity. Cigarette smoke exposure inhibits β2-agonist-mediated epithelial permeability increases, an effect reversed by blocking TGF-β signaling. β2-agonists enhance epithelial permeability via CFTR activation. TGF-β1 signaling inhibits β2-agonist-mediated CFTR activation and subsequent increased epithelial permeability, potentially limiting the ability of β2-agonists to facilitate paracellular transport in disease states unless TGF-β1 signaling is inhibited. |
---|---|
AbstractList | Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradient for serosal to mucosal fluid transport through its ability to both secrete Cl
−
and regulate paracellular permeability, but CFTR activity is attenuated in chronic bronchitis and in smokers. β
2
-adrenergic receptor (β
2
-AR) agonists are widely used for managing chronic obstructive pulmonary disease, and can activate CFTR, stimulate ciliary beat frequency, and increase epithelial permeability, thereby stimulating MCC. Patients with chronic airway diseases and cigarette smokers demonstrate increased transforming growth factor (TGF)-β1 signaling, which suppresses β
2
-agonist–mediated CFTR activation and epithelial permeability increases. Restoring CFTR function in these diseases can restore the ability of β
2
-agonists to enhance epithelial permeability. Human bronchial epithelial cells, fully redifferentiated at the air–liquid interface, were used for
14
C mannitol flux measurements, Ussing chamber experiments, and quantitative RT-PCR. β
2
-agonists enhance epithelial permeability by activating CFTR via the β
2
-AR/adenylyl cyclase/cAMP/protein kinase A pathway. TGF-β1 inhibits β
2
-agonist–mediated CFTR activation and epithelial permeability enhancement. Although TGF-β1 down-regulates both β
2
-AR and CFTR mRNA, functionally it only decreases CFTR activity. Cigarette smoke exposure inhibits β
2
-agonist–mediated epithelial permeability increases, an effect reversed by blocking TGF-β signaling. β
2
-agonists enhance epithelial permeability via CFTR activation. TGF-β1 signaling inhibits β
2
-agonist–mediated CFTR activation and subsequent increased epithelial permeability, potentially limiting the ability of β
2
-agonists to facilitate paracellular transport in disease states unless TGF-β1 signaling is inhibited. Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradient for serosal to mucosal fluid transport through its ability to both secrete Cl(-) and regulate paracellular permeability, but CFTR activity is attenuated in chronic bronchitis and in smokers. β2-adrenergic receptor (β2-AR) agonists are widely used for managing chronic obstructive pulmonary disease, and can activate CFTR, stimulate ciliary beat frequency, and increase epithelial permeability, thereby stimulating MCC. Patients with chronic airway diseases and cigarette smokers demonstrate increased transforming growth factor (TGF)-β1 signaling, which suppresses β2-agonist-mediated CFTR activation and epithelial permeability increases. Restoring CFTR function in these diseases can restore the ability of β2-agonists to enhance epithelial permeability. Human bronchial epithelial cells, fully redifferentiated at the air-liquid interface, were used for (14)C mannitol flux measurements, Ussing chamber experiments, and quantitative RT-PCR. β2-agonists enhance epithelial permeability by activating CFTR via the β2-AR/adenylyl cyclase/cAMP/protein kinase A pathway. TGF-β1 inhibits β2-agonist-mediated CFTR activation and epithelial permeability enhancement. Although TGF-β1 down-regulates both β2-AR and CFTR mRNA, functionally it only decreases CFTR activity. Cigarette smoke exposure inhibits β2-agonist-mediated epithelial permeability increases, an effect reversed by blocking TGF-β signaling. β2-agonists enhance epithelial permeability via CFTR activation. TGF-β1 signaling inhibits β2-agonist-mediated CFTR activation and subsequent increased epithelial permeability, potentially limiting the ability of β2-agonists to facilitate paracellular transport in disease states unless TGF-β1 signaling is inhibited. |
Author | Salathe, Matthias Dennis, John S Conner, Gregory E Unwalla, Hoshang J Ivonnet, Pedro |
Author_xml | – sequence: 1 givenname: Hoshang J surname: Unwalla fullname: Unwalla, Hoshang J organization: 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, and – sequence: 2 givenname: Pedro surname: Ivonnet fullname: Ivonnet, Pedro – sequence: 3 givenname: John S surname: Dennis fullname: Dennis, John S – sequence: 4 givenname: Gregory E surname: Conner fullname: Conner, Gregory E – sequence: 5 givenname: Matthias surname: Salathe fullname: Salathe, Matthias |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24978189$$D View this record in MEDLINE/PubMed |
BookMark | eNpVkEtr3TAQhUVJaR7tPqugZTZONXpcy5tAuPQRCGSTro0sj2w1tuRKuin3b-WH5DfV0JuSrubAnPkOZ07JUYgBCTkHdgWwUZ-TnbsrzkBUTAl9v31HTkAJVclGN0erZlJWoGRzTE5z_skYcA3wgRxz2dQadHNC9g_JhOximn0Y6JDi7zJSZ2yJqXp5BmpCT60fTMJSkOY5PiL1YfSdL7SMSE3nJ1_2NDr68swrM8Tgc8m0RIphNMEixcWvzsmbiS6YZjycfCTvnZkyfjrMM_Lj65eH7ffq7v7b7fbmrlo4F7aCHgWXzAqLXJpeO-2c4LyvzVrMKeicMBxBGtRK13aDrBE9130P2EDtUJyR67_cZdfN2FsMJZmpXZKfTdq30fj2_03wYzvEp1aKmnHFV8DlAZDirx3m0s4-W5wmEzDucgsbCVptGDSr9eJt1r-Q13-LP7dQiig |
ContentType | Journal Article |
Copyright | Copyright © 2015 by the American Thoracic Society 2015 |
Copyright_xml | – notice: Copyright © 2015 by the American Thoracic Society 2015 |
DBID | CGR CUY CVF ECM EIF NPM 7X8 5PM |
DOI | 10.1165/rcmb.2013-0538OC |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Anatomy & Physiology |
EISSN | 1535-4989 |
EndPage | 74 |
ExternalDocumentID | 24978189 |
Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: R01 HL066125 – fundername: NHLBI NIH HHS grantid: R01 HL060644 – fundername: NHLBI NIH HHS grantid: HL-089399 – fundername: NHLBI NIH HHS grantid: R01 HL089399 – fundername: NHLBI NIH HHS grantid: HL-060644 – fundername: NHLBI NIH HHS grantid: HL-066125 |
GroupedDBID | --- 0R~ 23M 2WC 3V. 53G 5GY 5RE 7X7 88A 88E 88I 8AF 8AO 8FE 8FH 8FI 8FJ 8R4 8R5 ABJNI ABUWG ACGFO ACGFS ACGOD ACPRK ADBBV AENEX AFFNX AFKRA AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AZQEC BAWUL BBNVY BENPR BES BHPHI BPHCQ BVXVI C45 CCPQU CGR CS3 CUY CVF DIK DWQXO E3Z EBS ECM EIF EJD EMOBN F3I F5P FRP FYUFA GNUQQ GX1 H13 HCIFZ HMCUK HZ~ J5H LK8 M0L M1P M2P M2Q M5~ M7P NPM O9- OBH OFXIZ OK1 OVD OVIDX P2P PQQKQ PROAC PSQYO PZZ Q2X RWL S0X SJN TAE TEORI THO TR2 UKHRP W8F WOQ YHG ZGI ZXP 7X8 5PM |
ID | FETCH-LOGICAL-p223c-1de3240c3ce24ad8f8ff322d7a154f51bf3a2e14ae8587c6e093d28dd1e917fe3 |
ISSN | 1044-1549 |
IngestDate | Tue Sep 17 21:26:57 EDT 2024 Sat Aug 17 02:32:36 EDT 2024 Sat Sep 28 08:06:18 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 1 |
Keywords | cystic fibrosis transmembrane conductance regulator epithelial permeability cigarette smoke transforming growth factor-β |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-p223c-1de3240c3ce24ad8f8ff322d7a154f51bf3a2e14ae8587c6e093d28dd1e917fe3 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://europepmc.org/articles/pmc4370252?pdf=render |
PMID | 24978189 |
PQID | 1641856019 |
PQPubID | 23479 |
PageCount | 10 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_4370252 proquest_miscellaneous_1641856019 pubmed_primary_24978189 |
PublicationCentury | 2000 |
PublicationDate | 2015-Jan 20150101 |
PublicationDateYYYYMMDD | 2015-01-01 |
PublicationDate_xml | – month: 01 year: 2015 text: 2015-Jan |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | American journal of respiratory cell and molecular biology |
PublicationTitleAlternate | Am J Respir Cell Mol Biol |
PublicationYear | 2015 |
Publisher | American Thoracic Society |
Publisher_xml | – name: American Thoracic Society |
References | 15463907 - J Cyst Fibros. 2004 Aug;3(3):189-91 19295125 - J Cell Sci. 2009 Apr 1;122(Pt 7):985-94 12609998 - J Biol Chem. 2003 May 2;278(18):15922-6 24040746 - Am J Respir Crit Care Med. 2013 Dec 1;188(11):1321-30 11479349 - J Gen Physiol. 2001 Aug;118(2):223-36 11138844 - Naunyn Schmiedebergs Arch Pharmacol. 2000 Dec;362(6):520-5 21454692 - J Biol Chem. 2011 Jun 3;286(22):19830-9 15361357 - Am J Physiol Lung Cell Mol Physiol. 2005 Jan;288(1):L77-83 15605377 - J Cell Physiol. 2005 Jun;203(3):564-72 2197151 - FASEB J. 1990 Jul;4(10):2709-17 16574992 - Am J Physiol Gastrointest Liver Physiol. 2006 Aug;291(2):G331-44 21825083 - Thorax. 2012 Jan;67(1):12-8 7775594 - J Cell Physiol. 1995 Jun;163(3):510-22 17591988 - J Gen Physiol. 2007 Jul;130(1):99-109 2604295 - Am Rev Respir Dis. 1989 Dec;140(6):1668-73 20156845 - J Physiol. 2010 Apr 15;588(Pt 8):1195-209 20639512 - J Biol Chem. 2010 Sep 24;285(39):29998-30007 20042712 - Am J Respir Cell Mol Biol. 2010 Nov;43(5):607-16 14729871 - J Histochem Cytochem. 2004 Feb;52(2):193-203 19996317 - J Biol Chem. 2010 Feb 12;285(7):4278-90 11078688 - Am J Physiol Cell Physiol. 2000 Dec;279(6):C1744-50 16984973 - J Cell Sci. 2006 Oct 15;119(Pt 20):4176-86 22047557 - N Engl J Med. 2011 Nov 3;365(18):1663-72 12621035 - J Biol Chem. 2003 May 9;278(19):17320-7 9493680 - Eur Respir J. 1997 Dec;10(12):2892-7 15265695 - Exp Cell Res. 2004 Aug 15;298(2):473-84 7224343 - Am Rev Respir Dis. 1981 Mar;123(3):320-6 22162907 - Am J Respir Cell Mol Biol. 2012 Apr;46(4):551-8 9875854 - Cell. 1998 Dec 23;95(7):1005-15 11707576 - Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14120-5 17369110 - Respir Physiol Neurobiol. 2007 Dec 15;159(3):324-30 7854206 - Microvasc Res. 1994 Sep;48(2):212-35 21990373 - FASEB J. 2012 Feb;26(2):533-45 16497995 - Am J Respir Crit Care Med. 2006 May 15;173(10):1139-44 21865736 - Cell Physiol Biochem. 2011;28(2):289-96 1362105 - Pulm Pharmacol. 1992 Dec;5(4):257-63 18366345 - Biochem J. 2008 Jul 1;413(1):135-42 12464936 - J Allergy Clin Immunol. 2002 Dec;110(6 Suppl):S275-81 12356577 - Am J Respir Cell Mol Biol. 2002 Oct;27(4):436-45 15626749 - Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L894-902 12502786 - Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):342-6 9922381 - Physiol Rev. 1999 Jan;79(1 Suppl):S175-91 19943936 - Respir Res. 2009;10:120 19818767 - Exp Mol Pathol. 2010 Feb;88(1):118-27 23671668 - PLoS One. 2013;8(5):e63167 |
References_xml | |
SSID | ssj0012811 |
Score | 2.3165448 |
Snippet | Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC... |
SourceID | pubmedcentral proquest pubmed |
SourceType | Open Access Repository Aggregation Database Index Database |
StartPage | 65 |
SubjectTerms | Adenylyl Cyclases - metabolism Adrenergic beta-2 Receptor Agonists - pharmacology Biological Transport, Active Bronchi - metabolism Bronchi - pathology Cells, Cultured Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Cystic Fibrosis Transmembrane Conductance Regulator - metabolism Epithelial Cells - metabolism Epithelial Cells - pathology Humans Original Research Permeability Receptors, Adrenergic, beta-2 - metabolism Respiratory Mucosa - metabolism Respiratory Mucosa - pathology Signal Transduction Smoking - adverse effects Smoking - metabolism Smoking - pathology Transforming Growth Factor beta1 - metabolism |
Title | Transforming growth factor-β1 and cigarette smoke inhibit the ability of β2-agonists to enhance epithelial permeability |
URI | https://www.ncbi.nlm.nih.gov/pubmed/24978189 https://search.proquest.com/docview/1641856019 https://pubmed.ncbi.nlm.nih.gov/PMC4370252 |
Volume | 52 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3dbtMwFLa6TULcINj42QaVkRg3VWB2nMS93KaOgUZBqJV6FyWOvVbQpGpT0HgcHmEPsmfCx3bSdNvF4Caqkiatcj7Z5-c730HoDck4iLSnXiBD32NJduhxrlJPsEAqoZgMU8O26IdnQ_ZpFIxarT8N1tKyTN-J33f2lfyPVfU5bVfokv0Hy9YP1Sf0Z21ffdQW1sf72bjyOiHev9ABdTl2A3S8g5PewTEltm1tYmbZlrKzmBbfQSVkPEknpomxY2W6TZnd3kK95KIAOV0j_SDzsekpkDPo3fgB6fWZXsulu63p2ta1n4YYxbxRyIcSgfk702oib8cpQFVGH-a_IK1vdsNiAZnsVdHq409g5DhKcTYvagcc2DmLilS8SuQaAs-80YXjWi5cgoMEjQSHrBblwGNdO2qoWrUDeguddgm2oyfcZm4nAN3eJkJQ1JiLaQrkPiAw-txpaK4pcve_xKfD8_N40BsNNtAWiC3CfIYPo5pGBIVIUpW_w-D9zWfeFbjc5N82HJrBY_TIRSL4yMLqCWrJfBvtHOXaWtNL_BYbbrCxzzZ68NlRMHbQZRN02IIOO9BdXxGsLYxrwGEDOOwAhzWEsEMOLhS-vlqBDZcFdmDDK7DhJtieouFpb3By5rn5Hd5MO53CI5kEuUfhC0n1KsAVV0rvH1mUaL9dBSRVfkIlYYnkAY9EKA-7fkZ5lhHZJZGS_jO0mRe5fIEwCxQTQtAuU4x1E8rNoIGUsCCjiSD-LnpdveZYr4-A6CSXxXIRkxDkmUIdyeyi5_a1xzMr5BJTGK9IuL4SrRmk_gJor69fySdjo8HO_EhHC3TvHr-7jx6uYP0SbZbzpXylPdkybaONaBS10dZxr__1W9sA6y-bu67P |
link.rule.ids | 230,314,780,784,885,27924,27925,31720,33745 |
linkProvider | Geneva Foundation for Medical Education and Research |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Transforming+growth+factor-%CE%B21+and+cigarette+smoke+inhibit+the+ability+of+%CE%B22-agonists+to+enhance+epithelial+permeability&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.au=Unwalla%2C+Hoshang+J&rft.au=Ivonnet%2C+Pedro&rft.au=Dennis%2C+John+S&rft.au=Conner%2C+Gregory+E&rft.date=2015-01-01&rft.eissn=1535-4989&rft.volume=52&rft.issue=1&rft.spage=65&rft.epage=74&rft_id=info:doi/10.1165%2Frcmb.2013-0538OC&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1044-1549&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1044-1549&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1044-1549&client=summon |