In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 283, No. 1 ( 2002-07-01), p. L188-L197
Abstract:
Inflammation, characterized by the presence of proinflammatory chemokines and neutrophils, is a hallmark of early airway disease in infants with cystic fibrosis (CF), although the underlying mechanisms remain poorly defined. In this study, we evaluated the role of NaCl and the ensuing hyperosmolar effect on tumor necrosis factor (TNF)-α signaling and apoptosis in macrophages. Incubation of mouse macrophages with NaCl activated p38 mapk and the p46 jnk and p54 jnk c- jun NH 2 -terminal kinase isoforms, but not p42 mapk/erk2 or Akt. Similar results were obtained with sorbitol, suggesting a general response to hyperosmolarity. Strikingly, the activation of p42 mapk/erk2 and Akt by TNF-α was also inhibited in the presence of NaCl. Because the activation of p42 mapk/erk2 and Akt has been associated with survival responses, we investigated the effect of NaCl on macrophage apoptosis. The results indicated a synergistic increase in apoptosis when macrophages were exposed to TNF-α in the presence of NaCl compared with stimulation with TNF-α alone or NaCl alone. Furthermore, pharmacological inhibition of p42 mapk/erk2 and Akt mimicked the effect of NaCl. Collectively, these findings indicate that modest elevations in NaCl differentially regulate the activation of mitogen-activated protein kinases and Akt and potentiate macrophage apoptosis. We speculate that augmentation of macrophage apoptosis in CF airways may result in decreased clearance of neutrophils and in deficiencies in the elimination of common CF pathogens.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00263.2001
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
1477300-4
SSG:
12
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