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Inflamm Res. 1999 Oct;48(10):533-8.

Cytokine mRNA decay is accelerated by an inhibitor of p38-mitogen-activated protein kinase.

Author information

1
Department of Biology, Amgen Inc., Boulder, CO 80301, USA.

Abstract

OBJECTIVE:

To identify the site(s) in tumor necrosis factor (TNFalpha), interleukin-6 (IL-6), and macrophage inflammatory protein-1alpha (MIP-1alpha) biosynthesis that is blocked by SB202190, a selective inhibitor of p38-mitogen activated protein kinase (p38).

MATERIALS:

Human blood monocytes isolated by centrifugal elutriation.

METHODS:

Monocytes were stimulated with lipopolysaccharide in the presence of 0, 0.3, 1 and 3 microM SB202190. Induced TNFalpha, IL-6, and MIP-1alpha protein and mRNA were measured by ELISA and quantitative RT-PCR, respectively. The half-lives of cytokine mRNA levels were determined following treatment of cells with actinomycin D or SB202190.

RESULTS:

SB202190 suppressed >60% of lipopolysaccharide-induced TNFalpha, IL-6, and MIP-1alpha protein and mRNA expression. Suppressed mRNA levels could be attributed to a >2 to 7-fold reduction in cytokine mRNA half-lives. In contrast, SB202190 did not destabilize mRNAs encoding interferon-induced gene 15 protein and glyceraldehyde-3-phosphate dehydrogenase.

CONCLUSIONS:

Specific mRNA destabilization represents an important and novel site of action for the cytokine suppressive effects of p38 inhibitors.

PMID:
10563470
DOI:
10.1007/s000110050499
[Indexed for MEDLINE]

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