| Inhibitory Effect of Farnesylthiosalicylic Acid on Mediators Release by Mast Cells: Preferential Inhibition of Prostaglandin D(2) and Tumor Necrosis Factor-α Release. | |
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MedLine Citation:
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PMID: 20706780 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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There is substantial evidence suggesting that the Ras inhibitor farnesylthiosalicylic acid (FTS) may modulate various aspects of immune function and inflammation in addition to its well known anti-cancer activity. In this regard, we have recently shown that FTS suppresses T lymphocyte-mediated immune responses. Mast cells (MC), the main effector cells in the elicitation of the allergic response, are known to secrete granule-associated mediators and to release prostaglandins and cytokines on FCεRI-cross-linking, thereby contributing to the pathogenesis of allergic diseases. We hypothesized that MC act as an additional target for FTS. In the present work we analyze the effects of FTS on MC degranulation, prostaglandin release, and cytokine release in vitro, and on the elicitation of IgE-mediated MC dependent cutaneous allergic inflammation in vivo. First we have established that FTS inhibited Ras activation in MC. Next, we have shown that FTS preferentially inhibited prostaglandin (PG) D(2) and tumor necrosis factor (TNF)-α release without having any significant effect on MC β-hexosaminidase secretion. In vivo administration of FTS inhibited the late phase of passive cutaneous anaphylaxis reaction. The time course of FTS-induced inhibition in vivo correlated with mediators release and not with degranulation. This data suggests that FTS may have an inhibitory effect on MC mediated allergic inflammation, and thus may be considered as a possible therapeutic modality. |
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Authors:
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Adam Mor; Ofer Ben-Moshe; Yoseph A Mekori; Yoel Kloog |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Inflammation Volume: 34 ISSN: 1573-2576 ISO Abbreviation: Inflammation Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600105 Medline TA: Inflammation Country: United States |
Other Details:
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Languages: eng Pagination: 314-8 Citation Subset: IM |
Affiliation:
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Department of Neurobiology, The George Weise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 61390, Israel, Adam.Mor@NYUMC.org. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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