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Role of mitogen-activated proteinkinase activation in the production of inflammatory mediators: differences between primary rat alveolar macrophages and macrophage cell lines.

Authors
Rao-K; Meighan-T; Bowman-L
Source
J Toxicol Environ Health, A 2002 May; 65(10):757-768
NIOSHTIC No.
20022510
Abstract
Stimulation of macrophages has been shown to activate all three families of mitogen activated protein kinases (MAPKs). However, variable results are reported in the literature with respect to the particular kinases activated with any given stimulus. In this study, the role of activation of MAPKs was examined in the production of inflammatory mediators by measuring the phosphorylation of the kinases and their ability to phosphorylate specific substrates in rat primary alveolar macrophages, a rat alveolar macrophage cell line (NR8383), and two mouse monocytic cell lines (RAW 264.7 and J774A.1). In the three cell lines examined, all three families of MAPKs were activated upon stimulation with either lipopolysaccharide (LPS) or LPS plus interferon-gamma; in contrast, only ERK1/2 was activated in primary rat alveolar macrophages upon stimulation with LPS. Inhibition of ERK1/2 activation by the MEK inhibitor PD98059 abrogated nitric oxide and tumor necrosis factor-alpha (TNF-alpha) production in primary rat alveolar macrophages, but the p38 inhibitor SB203580 had no effect on the production of these two inflammatory mediators. These observations indicate that MAPK activation is cell specific and explain some of the conflicting results reported in the literature. These studies emphasize the need to exercise caution in extrapolating data from cell lines to primary cells.
Keywords
Animal-studies; Animals; Cellular-reactions; Immunology; Pharmacology; Metabolism; Laboratory-animals; In-vitro-studies
Contact
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA
CODEN
JTEHD6
Publication Date
20020501
Document Type
Journal Article
Email Address
mir8@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
10
ISSN
0098-4108
NIOSH Division
HELD
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
WV
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