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PGJ2 inhibition of LPS-induced inflammatory mediator expression from rat alveolar macrophages.

Authors
Porter-DW; Wolfarth-M; Young-SH; Rao-MK; Meighan-T; Barger-M; Andrew-ME; Huffman-LJ
Source
J Toxicol Environ Health, A 2007 Jan; 70(23):1967-1976
NIOSHTIC No.
20032951
Abstract
Studies suggested that 15-deoxy--12,14-prostaglandin J2 (PGJ2) may exert anti-inflammatory effects, including in the lung. Thus, in vitro studies were conducted to (1) investigate whether PGJ2 inhibited the production of inflammatory mediators from lipopolysaccharide (LPS)-exposed primary rat alveolar macrophages (AM), and (2) investigate possible mechanisms underlying PGJ2-mediated inhibition of inflammatory mediator production. These studies determined that PGJ2 inhibited LPS-induced nitric oxide (NO) production in a concentration- and time-dependent manner. PGJ2-mediated inhibition of NO, as well as of tumor necrosis factor- (TNF-) and macrophage inflammatory protein-2 (MIP-2), was also determined to be dependent on the time of addition of PGJ2 relative to LPS, and suggested the PGJ2 inhibitory mechanism is an early event. PGJ2 was shown not to interfere with binding or internalization of LPS by AM, indicating this was not responsible for PGJ2 inhibitory effects. Another possible mechanism underlying PGJ2-mediated inhibition was via peroxisome proliferator-activated receptor- (PPAR-). However, biochemical studies suggested that PGJ2-mediated inhibition was not occurring through PPAR- dependent mechanism, and molecular studies further established that both LPS and PGJ2 decrease PPAR- mRNA expression. A third possible mechanism underlying PGJ2-mediated inhibition was by alteration of nuclear factor (NF)-B. Molecular studies confirmed that LPS stimulated NF-B mRNA expression, and PGJ2 reduced this stimulation, which is consistent with PGJ2 effect on LPS-induced production of NO, TNF- and MIP-2. Thus, data in this study established that PGJ2 inhibited LPS-induced inflammatory mediator production in rat AM, and this inhibition is mediated, at least in part, by reducing the expression of NF-B mRNA.
Keywords
Lung-disorders; Lung-irritants; Lung-disease; Pulmonary-disorders; Pulmonary-function; Pulmonary-system-disorders; Pulmonary-system; Dust-exposure; Dust-inhalation; Dust-particles; Dusts; Particle-aerodynamics; Particulate-dust; Air-contamination; Air-quality; Animal-studies; Biochemical-analysis
CODEN
JTEHD6
CAS No.
10102-43-9
Publication Date
20070101
Document Type
Journal Article
Email Address
pharber@ucla.edu
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
23
ISSN
1528-7394
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
WV
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