Inhibitory effect of farnesylthiosalicylic acid on mediators release by mast cells: Preferential inhibition of prostaglandin D 2 and tumor necrosis factor-α release

Adam Mor*, Ofer Ben-Moshe, Yoseph A. Mekori, Yoel Kloog

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 FCåRI-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.

Original languageEnglish
Pages (from-to)314-318
Number of pages5
JournalInflammation
Volume34
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Farnesylthiosalicylic acid
  • Mast cell
  • Tumor necrosis factor

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