Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-α

被引:91
作者
Booth, BW
Adler, KB
Bonner, JC
Tournier, F
Martin, LD [1 ]
机构
[1] N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA
[2] NIEHS, Res Triangle Pk, NC 27709 USA
[3] Univ Paris 07, Lab Cytophysiol & Toxicol Cellulaire, Paris, France
关键词
D O I
10.1165/ajrcmb.25.6.4659
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [H-3]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response.
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收藏
页码:739 / 743
页数:5
相关论文
共 32 条
[1]   Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways [J].
Alimam, MZ ;
Piazza, FM ;
Selby, DM ;
Letwin, N ;
Huang, L ;
Rose, MC .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 22 (03) :253-260
[2]   Proliferation and number of Clara cell 10-kDa protein (CC10)-reactive epithelial cells and basal cells in normal, hyperplastic and metaplastic bronchial mucosa [J].
Barth, PJ ;
Koch, S ;
Müller, B ;
Unterstab, F ;
von Wichert, P ;
Moll, R .
VIRCHOWS ARCHIV, 2000, 437 (06) :648-655
[3]   EXPRESSION OF THE TRANSFORMING GROWTH FACTOR-ALPHA EPIDERMAL GROWTH-FACTOR RECEPTOR PATHWAY IN NORMAL HUMAN-BREAST EPITHELIAL-CELLS [J].
BATES, SE ;
VALVERIUS, EM ;
ENNIS, BW ;
BRONZERT, DA ;
SHERIDAN, JP ;
STAMPFER, MR ;
MENDELSOHN, J ;
LIPPMAN, ME ;
DICKSON, RB .
ENDOCRINOLOGY, 1990, 126 (01) :596-607
[4]  
BOOTH B, 2001, AM J RESP CRIT CARE, V163, pA738
[5]  
COFFEY RJ, 1992, YALE J BIOL MED, V65, P693
[6]   Acute epithelial injury in the rat small intestine in vivo is associated with expanded expression of transforming growth factor alpha and beta [J].
Dignass, AU ;
Stow, JL ;
Babyatsky, MW .
GUT, 1996, 38 (05) :687-693
[7]   Apoptosis, proliferation, and expression of bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics [J].
Druilhe, A ;
Wallaert, B ;
Tsicopoulos, A ;
Silva, JRLE ;
Tille-Leblond, I ;
Tonnel, AB ;
Pretolani, M .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1998, 19 (05) :747-757
[8]  
Farbman AI, 1996, J NEUROBIOL, V30, P267, DOI 10.1002/(SICI)1097-4695(199606)30:2<267::AID-NEU8>3.3.CO
[9]  
2-H
[10]   Tumor necrosis factor-α stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro [J].
Fischer, BM ;
Rochelle, LG ;
Voynow, JA ;
Akley, NJ ;
Adler, KB .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1999, 20 (03) :413-422