Zileuton, a leukotriene synthesis inhibitor in the management of chronic asthma

SummaryTo learn whether glucocorticoids inhibit prostaglandin (PG) production in vascular endothelial cells, we investigated the effects of glucocorticoids on PG synthesis by cultured human umbilical vein endothelial cells (EC). Pretreatment of EC with dexamethasone (DX, 10-9 to 5 x 10-5 M) caused a dose-dependent inhibition of PGI2 production when PG synthesis from endogenous arachidonate was stimulated by human thrombin (0.25-2 U/ml) or ionophore A 23187 (1-5 μM). The inhibition was detectable at 10-7 M DX and maximal at 10-5 M (4.0 ± 0.7 vs. control: 7.7 ± 1.9 ng/ml, mean ± S.D., P <0.01). The production of PGE2 and the release of radiolabelled arachidonate (AA) from prelabelled cells were similarly inhibited. Prolonged incubation of EC with glucocorticoids was required to inhibit PG production or arachidonate release: ranging from 8% inhibition at 5 h to 44% at 38 h. In contrast, prostaglandin formation from exogenous AA was not altered by DX treatment. When thrombin or ionophore-stimulated EC were restimulated with exogenous AA (25 μM), DX-treated cells released more PGI2 than control cells (5.7 ± 0.5 vs. 4.1 ± 0.6 ng/ml, P <0.01). Both the decrease in PGI2 production after thrombin/ionophore and the increase after re-stimulation with AA were blunted in the presence of the protein synthesis inhibitor cycloheximide (0.1-0.2 μg/ml). Thus, incubation of EC with glucocorticoids inhibits PG production at the step of phospholipase activation. The time requirement for these steroid effects and their blunting by cycloheximide are consistent with the induction of regulatory proteins, possibly lipocortins, in endothelial cells.

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Faculty Opinions recommendation of Behavioral impairments caused by injections of the protein synthesis inhibitor anisomycin after contextual retrieval reverse with time.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007563.207733 ◽

2004 ◽

Author(s):

James L. McGaugh

Keyword(s):

Protein Synthesis ◽

Protein Synthesis Inhibitor ◽

Synthesis Inhibitor ◽

Contextual Retrieval ◽

Behavioral Impairments

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Faculty Opinions recommendation of Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13333956.14700054 ◽

2011 ◽

Author(s):

Dan Conrad

Keyword(s):

Mast Cell ◽

Mouse Model ◽

Chronic Asthma ◽

Cell Axis ◽

Ifn Γ

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Faculty Opinions recommendation of Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718277738.793491004 ◽

2014 ◽

Author(s):

Andrew Tonkin

Keyword(s):

Apolipoprotein B ◽

Ldl Cholesterol ◽

Familial Hypercholesterolaemia ◽

Controlled Trial ◽

Synthesis Inhibitor ◽

Double Blind ◽

Double Blind Placebo ◽

Homozygous Familial Hypercholesterolaemia

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Faculty Opinions recommendation of Effect of nintedanib on airway inflammation and remodeling in a murine chronic asthma model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733275363.793546224 ◽

2018 ◽

Author(s):

Raymond Penn

Keyword(s):

Airway Inflammation ◽

Chronic Asthma ◽

Asthma Model

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PROTECTIVE EFFECT OF POLYPEPTIDE AND AMINO ACIDS ON THE DEVELOPMENT OF THE NERVOUS TISSUE CULTURE IN THE PRESENCE OF CYCLOPHOSPHAMIDE

Токсикологический вестник ◽

10.36946/0869-7922-2017-2-22-26 ◽

2017 ◽

pp. 22-26

Author(s):

V. B. Dolgo-Saburov ◽

N. I. Chalisova ◽

L. V. Lyanginen ◽

E. S. Zalomaeva

Keyword(s):

Amino Acids ◽

Cell Proliferation ◽

Tissue Culture ◽

Protective Effect ◽

Organotypic Culture ◽

Inhibitory Effect ◽

Mustard Gas ◽

Synthesis Inhibitor ◽

Combined Administration ◽

The Central Nervous System

In an organotypic culture, an investigation was conducted into combined effects of cyclophosphamide DNA as synthesis inhibitor used to model a resorptive action of mustard gas, and cortexin polypeptide or each of 20 encoded amino acids on the development of cell proliferation in cerebral cortex explants of the rat. The combined administration of cyclophosphamide together with cortexin or with each of the 20 encoded amino acids, except glycine, showed suppression of the cytostatic agent inhibitory effect. Thus, cortexin and amino acids have a protective effect on cell proliferation in the tissue culture of the central nervous system under the action of mustardlike substances.

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