In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 286, No. 1 ( 2004-01), p. L4-L14
Abstract:
In the present study, IFN-γ exposure to primary cultures of rat type II epithelial cells (TIIP) upregulated membrane expression of the common γ-chain of the IL-2 receptor (∼2.5- to 4-fold increase) and redistributed receptor affinity in TIIP, as assessed by Western blot, cell, and tissue histochemistry and Scatchard analysis. As for restitution processes of the lung epithelium, functionality of IL-2R on TIIP was conditional to IFN-γ exposure: 1) IFN-γ priming promoted a fivefold increase of IL-2-driven TIIP locomotion ( P 〈 0.05 vs. control at 100 U/ml) and 2) IFN-γ coincubation with IL-2 reduced bleomycin-induced TIIP apoptosis in vitro by 25% (caspase-3 activity) and by ∼70% (TdT-mediated dUTP nick end labeling/4′,6′-diamidino-2-phenylindole assay) as well as in vivo by ∼90% (caspase-3 activity; P 〈 0.05 vs. control). Sustained p42/44 extracellular signal-regulated kinase activity played a protective role in this process, whereas specific inhibition by PD-98059 (50 μM) significantly reversed bleomycin-induced TIIP apoptosis ( P 〈 0.05 vs. control). From these in vitro and in vivo data, it is proposed that combinations of IFN-γ and IL-2 can drive repair activity of TIIP by stimulating migration and preventing programmed cell death, both of which are speculated to be very fast restitution events after oxidant-induced acute lung injury.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00367.2002
Language:
English
Publisher:
American Physiological Society
Publication Date:
2004
detail.hit.zdb_id:
1477300-4
SSG:
12
