科研之友
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摘要
Aliphatic n-alkanols are a family of ubiquitous substances that display general anesthetic properties in accordance to their degree of hydrophobicity. In addition, the immunomodulatory activity of one of its members, ethanol, has long been recognized. We reasoned that because unbranched aliphatic n-alkanols are structurally very similar they might have an immunological impact that mirrors their anesthetic potency. We report the impact of the homologous C-1-C-12 alcohol series on the ability of activated primary human lymphocytes to produce IFN-gamma. Methanol enhanced IFN-gamma production whereas C-2-C-10 alcohols reduced the release of this cytokine. The activity of the n-alkanol series was observed within a wide concentration window ranging from millimolar levels for short chain alcohols to micromolar amounts for C-7-C-10 alcohols. There was a clear correlation between immunomodulatory activity and hydrophobicity of the compounds, but a cutoff effect was evident at C-11. n-Alkanols were shown to act downstream of the cell membrane because T cell receptor early signaling was preserved. The activation of the nuclear factor of activated T cells (NFAT) was down-regulated progressively in accordance to the size of the n-alkanol aliphatic chains with a clear downward trend that was interrupted at C-11. The nuclear factor-kappa B (NF-kappa B) signaling was also compromised, but the cutoff appeared earlier at C-10. The pattern of immunomodulation and transcriptional dysregulation induced by the n-alkanol series suggested the existence of interaction pockets of defined dimensions within intracellular targets that compromise the activation of NFAT and NF-kappa B transcription factors and ultimately modulate the effector function of the T lymphocyte.
- 出版日期2013-8-23
