help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fischer, B. M.
Right arrow Articles by Adler, K. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fischer, B. M.
Right arrow Articles by Adler, K. B.

Am. J. Respir. Cell Mol. Biol., Volume 20, Number 3, March, 1999 413-422

Tumor Necrosis Factor-alpha Stimulates Mucin Secretion and Cyclic GMP Production by Guinea Pig Tracheal Epithelial Cells In Vitro

Bernard M. Fischer, Lori G. Rochelle, Judith A. Voynow, Nancy J. Akley, and Kenneth B. Adler

Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh; Cystic Fibrosis/Pulmonary Research Center, University of North Carolina, Chapel Hill; and Division of Pediatric Pulmonary Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina

Tumor necrosis factor (TNF)-alpha , a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion of mucin by airway epithelial cells in vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha -induced mucin secretion using guinea pig tracheal epithelial (GPTE) cells in air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated mucin secretion in a concentration-dependent manner, with maximal effects at 10 to 15 ng/ml (286 to 429 U/ml). The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (PKG). TNF-alpha increased production of nitrite and nitrate by GPTE cells; both mucin secretion and cGMP production were attenuated by NG-monomethyl-L-arginine (1 mM), a competitive inhibitor of nitric oxide synthase (NOS), or by the GC-S inhibitor LY83583 (50 µM); and mucin secretion in response to TNF-alpha or to the cGMP analogue dibutyryl cGMP (100 and 500 µM) was attenuated by the specific PKG inhibitor KT5823 (1 µM). Increased mucin secretion and increased cGMP production in response to TNF-alpha both appeared to be mediated by a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC), and by protein kinase C (PKC), since both responses were attenuated by either D609 (10 and 20 µg/ml), a specific PC-PLC inhibitor, or by each of three PKC inhibitors: Calphostin C (0.3 and 0.5 µM), bisindoylmaleimide (GF 109203X, Go 6850; 20 nM), or Ro31-8220 (10 µM). Collectively, the results suggest that TNF-alpha stimulates secretion of mucin by GPTE cells via a mechanism(s) dependent on PC-PLC and PKC, and involving activation of NOS, generation of NO, production of cGMP, and activation of PKG.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. H. Abdullah and C. W. Davis
Regulation of airway goblet cell mucin secretion by tyrosine phosphorylation signaling pathways
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L591 - L599.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J.-A. Park, F. He, L. D. Martin, Y. Li, B. N. Chorley, and K. B. Adler
Human Neutrophil Elastase Induces Hypersecretion of Mucin from Well-Differentiated Human Bronchial Epithelial Cells in Vitro via a Protein Kinase C{delta}-Mediated Mechanism
Am. J. Pathol., September 1, 2005; 167(3): 651 - 661.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Lu, E. P. Lillehoj, and K. C. Kim
Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells
Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L52 - L60.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Subbaramaiah, K. Yoshimatsu, E. Scherl, K. M. Das, K. D. Glazier, D. Golijanin, R. A. Soslow, T. Tanabe, H. Naraba, and A. J. Dannenberg
Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Inflammatory Bowel Disease: EVIDENCE FOR INVOLVEMENT OF THE TRANSCRIPTION FACTOR Egr-1
J. Biol. Chem., March 26, 2004; 279(13): 12647 - 12658.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Gray, R. Coakley, A. Hirsh, D. Thornton, S. Kirkham, J.-S. Koo, L. Burch, R. Boucher, and P. Nettesheim
Regulation of MUC5AC mucin secretion and airway surface liquid metabolism by IL-1{beta} in human bronchial epithelia
Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L320 - L330.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Page, J. Li, L. Zhou, S. Iasvoyskaia, K. C. Corbit, J.-W. Soh, I. B. Weinstein, A. R. Brasier, A. Lin, and M. B. Hershenson
Regulation of Airway Epithelial Cell NF-{kappa}B-Dependent Gene Expression by Protein Kinase C{delta}
J. Immunol., June 1, 2003; 170(11): 5681 - 5689.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. D. Conway, T. Bartolotta, L. H. Abdullah, and C. W. Davis
Regulation of mucin secretion from human bronchial epithelial cells grown in murine hosted xenografts
Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L945 - L954.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Huang, T. Dudez, I. Scerri, M. A. Thomas, B. N. G. Giepmans, S. Suter, and M. Chanson
Defective Activation of c-Src in Cystic Fibrosis Airway Epithelial Cells Results in Loss of Tumor Necrosis Factor-alpha -induced Gap Junction Regulation
J. Biol. Chem., February 28, 2003; 278(10): 8326 - 8332.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. M. Matheson, R. Lemus, R. W. Lange, M. H. Karol, and M. I. Luster
Role of Tumor Necrosis Factor in Toluene Diisocyanate Asthma
Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 396 - 405.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. R. Meusel, K. E. Kehoe, and F. Imani
Protein Kinase R Regulates Double-Stranded RNA Induction of TNF-{alpha} But Not IL-1{beta} mRNA in Human Epithelial Cells
J. Immunol., June 15, 2002; 168(12): 6429 - 6435.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
C. A. Pettersen and K. B. Adler
Airways Inflammation and COPD* : Epithelial-Neutrophil Interactions
Chest, May 1, 2002; 121(5_suppl): 142S - 150S.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
G. D. Leikauf, M. T. Borchers, D. R. Prows, and L. G. Simpson
Mucin Apoprotein Expression in COPD*
Chest, May 1, 2002; 121(5_suppl): 166S - 182S.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. W. Booth, K. B. Adler, J. C. Bonner, F. Tournier, and L. D. Martin
Interleukin-13 Induces Proliferation of Human Airway Epithelial Cells In Vitro via a Mechanism Mediated by Transforming Growth Factor-alpha
Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 739 - 743.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. B. Adler and Y. Li
Airway Epithelium and Mucus . Intracellular Signaling Pathways for Gene Expression and Secretion
Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 397 - 400.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Chen, Y. H. Zhao, and R. Wu
Differential Regulation of Airway Mucin Gene Expression and Mucin Secretion by Extracellular Nucleotide Triphosphates
Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 409 - 417.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B. L. Tepperman, Q. Chang, and B. D. Soper
Protein Kinase C Mediates Lipopolysaccharide- and Phorbol-Induced Nitric-Oxide Synthase Activity and Cellular Injury in the Rat Colon
J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 1249 - 1257.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Xie, A. Reusse, J. Dai, K. Zay, J. Harnett, and A. Churg
TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappa B-dependent mechanism
Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L608 - L614.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Reibman, A. T. Talbot, Y. Hsu, G. Ou, J. Jover, D. Nilsen, and M. H. Pillinger
Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases
J. Immunol., August 1, 2000; 165(3): 1618 - 1625.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. M. Krunkosky, B. M. Fischer, L. D. Martin, N. Jones, N. J. Akley, and K. B. Adler
Effects of TNF-alpha on Expression of ICAM-1 in Human Airway Epithelial Cells In Vitro . Signaling Pathways Controlling Surface and Gene Expression
Am. J. Respir. Cell Mol. Biol., June 1, 2000; 22(6): 685 - 692.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Perrais, P. Pigny, M.-P. Ducourouble, D. Petitprez, N. Porchet, J.-P. Aubert, and I. Van Seuningen
Characterization of Human Mucin Gene MUC4 Promoter. IMPORTANCE OF GROWTH FACTORS AND PROINFLAMMATORY CYTOKINES FOR ITS REGULATION IN PANCREATIC CANCER CELLS
J. Biol. Chem., August 10, 2001; 276(33): 30923 - 30933.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Li, L. D. Martin, G. Spizz, and K. B. Adler
MARCKS Protein Is a Key Molecule Regulating Mucin Secretion by Human Airway Epithelial Cells in Vitro
J. Biol. Chem., October 26, 2001; 276(44): 40982 - 40990.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1999 American Thoracic Society.