JNK1 and AP-1 regulate PMA-inducible squamous differentiation marker expression in Clara-like H441 cells
1 Department of Environmental Health Sciences, The Johns Hopkins University School of Public Health, Baltimore 21205; 2 University of Maryland School of Pharmacy, Baltimore 21201; and 3 Greenbaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201 Exposure of dista...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 282; no. 2; pp. 215 - L225 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.02.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Environmental Health Sciences, The Johns
Hopkins University School of Public Health, Baltimore 21205;
2 University of Maryland School of Pharmacy, Baltimore 21201;
and 3 Greenbaum Cancer Center, University of Maryland
School of Medicine, Baltimore, Maryland 21201
Exposure of distal bronchiolar region to
various toxicants and pollutants suppresses Clara cell differentiation
marker expression and greatly enhances the induction of squamous cell
differentiation (SCD). Here, we demonstrate for the first time phorbol
13-myristate 12-acetate (PMA)-inducible expression of SCD markers,
SPRRs, in Clara-like H441 cells. The transcriptional
stimulation of human SPRR1B expression is mainly mediated by
a 150- to 84-bp region that harbors two critical activator protein
(AP)-1 sites. In unstimulated cells, the 150- to 84-bp region is
weakly bound by AP-1 proteins, mainly JunD and Fra1. However, PMA
prominently induced the binding of JunB and Fra1. Consistent with this,
overexpression of wild-type Jun proteins upregulated the
SPRR1B promoter activity. Conversely, a c- jun mutant
suppressed both basal and PMA-inducible reporter gene expression.
Intriguingly, overexpression of fra 2 suppressed PMA-inducible reporter activity, whereas fra 1 significantly
enhanced basal level activity, indicating an opposing role for these
proteins in SPRR1B expression in a manner similar to that
observed in proximal tracheobronchial epithelial cells (BEAS-2B clone
S6). Interestingly, unlike in S6 cells, a catalytically inactive c-Jun
NH 2 -terminal kinase (JNK) 1 mutant significantly reduced
the PMA-inducible SPRR1B promoter activity in H441 cells.
Thus either temporal expression and/or spatial activation of AP-1
proteins by JNK1 might contribute to the induction of SCD in Clara cells.
small proline rich proteins; airway epithelium; transcriptional
regulation; mitogen-activated protein kinases; Jun/Fos; c-Jun
NH 2 -terminal kinase 1; activator protein 1 |
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ISSN: | 1040-0605 1522-1504 |
DOI: | 10.1152/ajplung.00125.2001 |