Abbreviation: LT[Csub4] = leukotriene [Csub4] The goal of this investigation was to determine the effect(s) of the bacterial composing lipopolysaccharide.

Abbreviation: LT[Csub4] = leukotriene [Csub4]

The goal of this investigation was to determine the effect(s) of the bacterial composing lipopolysaccharide, on leukotriene [C.sub.4] (LT[Csub4]) synthase gene expression in mononuclear phagocytes. Lipopolysaccharide treatment for 7 days issueed in decreased stimulated LT[C.sub.4] release from the monocyte-like enclosed space line, THP-1. Reverse transcriptase polymerase chain reaction studies demonstrated expression of the putative lipopolysaccharide receptor, Toll-like receptor 4 in the one and the other THP-1 cells and the eosinophil-like lonely dwelling line, AML14.3D10. Conditioning with high-dose lipopolysaccharide deductioned in cell-specific down-regulation of LTC4 synthase harbinger RNA in THP-1 cells, yet not in AML14.3D10 cells. Treatment of THP-1 enclosed spaces with lipopolysaccharide demonstrated that the inhibitory result is serotype-independent, dose-dependent (at doses from 0001 to 100 ng/mL) and time-dependent, occurring as early as 4 h after position Actinomycin-D studies indicate that lipopolysaccharide does not accelerate the rate of LT[Csub4] synthase emissary RNA decay. Transient transfection of THP-1 solitary abode; squalids with a luciferase reporter set up containing the first 1.35 kilobases of the LT[Csub4] synthase promoter demonstrated that lipopolysaccharide decreases LT[Csub4] synthase promoter activity. Treatment of THP-1 confined apartments with a specific inhibitor of nuclear factor-[kappa]B ensueed in abrogation of the efficiency of lipopolysaccharide on LT[C.sub.4] synthase gene expression. Induced activation of nuclear factor-[kappa]B consequence ed in a time-dependent decrease in LT[Csub4] synthase intelligencer RNA. Cell-specific lipopolysaccharide modulation of LT[Csub4] synthase gene expression may have important implications for understanding the part of bacterial exposure in the pathogenesis of inflammatory lung diseases, in the same state [i]or[/i] condition as asthma.

* From the Department of Medicine, Veterans Affairs San Diego Healthcare a whole and the University of California, San Diego, CA. Supported from the Tobacco Related Disease Research Program of California (8KT-0126) and the Department of Veterans Affairs. Reproduction of this article is prohibited without written permission from the American corporation of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Timothy D Bixby, MD Veterans Affairs San Diego Healthcare theory 3350 La Jolla Village Dr 111J San Diego, CA 92161; e-mail: tbigby@ucsd.edu

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