Back to Search
Start Over
Neutrophil defensins enhance lung epithelial wound closure and mucin gene expression in vitro.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2004 Feb; Vol. 30 (2), pp. 193-201. Date of Electronic Publication: 2003 Jul 18. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Cell Line
Cell Movement
Enzyme Activation
Epithelial Cells cytology
ErbB Receptors metabolism
Humans
MAP Kinase Signaling System physiology
Mitogen-Activated Protein Kinases metabolism
Mucins genetics
Respiratory Mucosa cytology
Anti-Infective Agents metabolism
Epithelial Cells metabolism
Mucins metabolism
Neutrophils metabolism
Respiratory Mucosa pathology
alpha-Defensins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1044-1549
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 12871849
- Full Text :
- https://doi.org/10.1165/rcmb.2002-0267OC