help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on July 18, 2003, doi:10.1165/rcmb.2002-0267OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0267OCv1
30/2/193    most recent
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 Aarbiou, J.
Right arrow Articles by Hiemstra, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aarbiou, J.
Right arrow Articles by Hiemstra, P. S.
American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 193-201, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2002-0267OC

Neutrophil Defensins Enhance Lung Epithelial Wound Closure and Mucin Gene Expression In Vitro

Jamil Aarbiou, Renate M. Verhoosel, Sandra van Wetering, Willem I. de Boer, J. Han J. M. van Krieken, Sergey V. Litvinov, Klaus F. Rabe and Pieter S. Hiemstra

Departments of Pulmonology and Pathology, Leiden University Medical Center, Leiden; and Department of Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

Address correspondence to: Jamil Aarbiou, Dept. of Pulmonology, C3-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: j.aarbiou{at}lumc.nl

Human airways are frequently exposed to potentially harmful agents that cause tissue injury. Upon such injury, a repair process is initiated that comprises cell migration, proliferation, and differentiation. We have previously shown that human neutrophil defensins (human neutrophil peptides 1–3 [HNP1–3]) induce airway epithelial cell proliferation. Because of the role of cell proliferation in epithelial wound repair, we investigated the effect of HNP1–3 on airway epithelial wound closure and mucin gene expression in vitro. Using NCI-H292 airway epithelial cell cultures, we demonstrated that HNP1–3 cause a dose- and time-dependent increase of wound closure as well as increased cell migration. Furthermore, HNP1–3 caused a biphasic activation of the mitogen-activated protein kinase extracellular-regulated kinase 1 and 2 (ERK1/2). Both the effects of HNP1–3 on wound closure and ERK1/2 activation were blocked by specific inhibitors of the mitogen-activated protein kinase kinase MEK, whereas inhibitors of epidermal growth factor receptor tyrosine kinase, phosphatidylinositol 3-kinase, and Src did block defensin-enhanced wound closure but not ERK1/2 activation. Finally, HNP1–3 increased mRNA encoding the mucins MUC5B and MUC5AC, suggesting a role for defensins in mucous cell differentiation. These results indicate that neutrophil defensins increase epithelial wound repair in vitro, which involves migration and proliferation, and mucin production. Neutrophil defensin–enhanced wound repair appears to require epidermal growth factor receptor activation and downstream signaling pathways.

Abbreviations: 5-bromo-2-deoxyuridin, BrdU • epidermal growth factor, EGF • extracellular-regulated kinase 1 and 2, ERK1/2 • fetal calf serum, FCS • human neutrophil peptide 1–3, HNP1–3 • c-jun N-terminal kinase, JNK • mitogen-activated protein kinase, MAPK • primary bronchial epithelial cells, PBEC • phosphate-buffered saline, PBS • polymerase chain reaction, PCR • phosphatidylinositol 3-kinase, PI-3K • transforming growth factor-{alpha}, TGF-{alpha} • tumor necrosis factor-{alpha}, TNF-{alpha}




This article has been cited by other articles:


Home page
 ChestHome page
L. Petecchia, F. Sabatini, L. Varesio, A. Camoirano, C. Usai, A. Pezzolo, and G. A. Rossi
Bronchial Airway Epithelial Cell Damage Following Exposure to Cigarette Smoke Includes Disassembly of Tight Junction Components Mediated by the Extracellular Signal-Regulated Kinase 1/2 Pathway
Chest, June 1, 2009; 135(6): 1502 - 1512.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Li, H. Y. Zhu, and R. W. Beuerman
Stimulation of Specific Cytokines in Human Conjunctival Epithelial Cells by Defensins HNP1, HBD2, and HBD3
Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 644 - 653.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. J. Choi, Y.-S. Chung, H. J. Kim, U. Y. Moon, Y. H. Choi, I. Van Seuningen, S. J. Baek, H.-G. Yoon, and J.-H. Yoon
Signal Pathway of 17{beta}-Estradiol-Induced MUC5B Expression in Human Airway Epithelial Cells
Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 168 - 178.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
H. Ishimoto, H. Mukae, N. Sakamoto, M. Amenomori, T. Kitazaki, Y. Imamura, H. Fujita, H. Ishii, S. Nakayama, K. Yanagihara, et al.
Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin
J. Antimicrob. Chemother., January 1, 2009; 63(1): 109 - 114.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
L. C. Huang, R. L. Redfern, S. Narayanan, R. Y. Reins, and A. M. McDermott
In Vitro Activity of Human {beta}-Defensin 2 against Pseudomonas aeruginosa in the Presence of Tear Fluid
Antimicrob. Agents Chemother., November 1, 2007; 51(11): 3853 - 3860.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
R. Shaykhiev and R. Bals
Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis
J. Leukoc. Biol., July 1, 2007; 82(1): 1 - 15.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
E. Puchelle, J.-M. Zahm, J.-M. Tournier, and C. Coraux
Airway Epithelial Repair, Regeneration, and Remodeling after Injury in Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2006; 3(8): 726 - 733.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Li, M. Raghunath, D. Tan, R. R. Lareu, Z. Chen, and R. W. Beuerman
Defensins HNP1 and HBD2 Stimulation of Wound-Associated Responses in Human Conjunctival Fibroblasts.
Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3811 - 3819.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
J. Sodek, A. P. Batista Da Silva, and R. Zohar
Osteopontin and Mucosal Protection
Journal of Dental Research, May 1, 2006; 85(5): 404 - 415.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. B. Buck, P. M. Day, C. D. Thompson, J. Lubkowski, W. Lu, D. R. Lowy, and J. T. Schiller
Human {alpha}-defensins block papillomavirus infection
PNAS, January 31, 2006; 103(5): 1516 - 1521.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. C. Rose and J. A. Voynow
Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease
Physiol Rev, January 1, 2006; 86(1): 245 - 278.
[Abstract] [Full Text] [PDF]

Home page
 ptjournalHome page
C. Godbout and J. Frenette
Periodic Direct Current Does Not Promote Wound Closure in an In Vitro Dynamic Model of Cell Migration
Physical Therapy, January 1, 2006; 86(1): 50 - 59.
[Abstract] [Full Text] [PDF]

Home page
 ptjournalHome page
N. I Spielholz
Invited Commentary
Physical Therapy, January 1, 2006; 86(1): 59 - 62.
[Full Text]

Home page
 J. Leukoc. Biol.Home page
S. van Wetering, G. S. Tjabringa, and P. S. Hiemstra
Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells
J. Leukoc. Biol., April 1, 2005; 77(4): 444 - 450.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society. 		  Tobacco