Resistance to silica-induced lung fibrosis in senescent rats: role of alveolar macrophages and tumor necrosis factor-alpha (TNF).

Abstract:

:The purpose of the present study was to investigate the effect of aging on silica-induced lung toxicity. In young animals silica induced a significant increase in bronchoalveolar lavage tumor necrosis factor-alpha (TNF), lactate dehydrogenase as well as in cell numbers, which correlate with increased collagen deposition and silicotic nodules formations. In old rats, however, no changes in bronchoalveolar lavage or lung parameters were observed following silica instillation. These in vivo results were also confirmed in vitro, where silica failed to induce TNF release in alveolar macrophages obtained from old animals. This defective response to silica could be explained with defective protein kinase C translocation, due to a reduction in its anchoring protein RACK-1 with aging. Overall, these data indicate that the understanding of the molecular mechanisms undelaying toxicity is crucial to define the influence of age on the toxic response and progression of the disease.

journal_name

Mech Ageing Dev

authors

Corsini E,Giani A,Peano S,Marinovich M,Galli CL

doi

10.1016/j.mad.2003.11.002

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

145-6

issue

2

eissn

0047-6374

issn

1872-6216

pii

S0047637403002215

journal_volume

125

pub_type

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