Terfenadine antagonism against interleukin-4-modulated gene expression of T cell cytokines

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:121

Article

Maeda, A ; Matsushita, K ; Yamazaki, F ; Kawada, A ; Tezuka, T ; Aragane, Y

关键词: activator protein-1;    JunB;    terfenadine;    T helper 1;    T helper 2;   

DOI  :  10.1046/j.1523-1747.2003.12401.x

来源: Elsevier

【 摘 要 】

Here, we investigated whether an anti-allergy drug, terfenadine, affects interleukin-4-modulated cytokine expression in peripheral T cells. Peripheral blood T cells were first stimulated with recombinant interleukin-4 and then tested for modulation of the mRNA of a panel of cytokines using the reverse transcription-polymerase chain reaction followed by Southern blot analysis. It was found that T cells constitutively expressed mRNA specific to T helper 1 cytokines (interleukin-2, interferon-gamma, tumor necrosis factor-alpha), which was markedly downregulated upon stimulation with interleukin-4, whereas mRNA for T helper 2 cytokines such as interleukins 4, 5, and 6 was induced in response to interleukin-4. Interestingly, the interleukin-4-induced expression of all T helper 2 cytokines examined was markedly downregulated by terfenadine. Among T helper 1 cytokines, interleukin-4-mediated suppression of tumor necrosis factor-alpha was not affected by terfenadine, which, however, markedly restored mRNA expression of interferon-gamma or interleukin-2. Electrophoretic mobility shift assays using [P-32]-labeled synthetic oligonucleotides encoding the consensus binding motif of activator protein-1 demonstrated that interleukin-4-induced binding of activator protein-1 composed of JunB was interfered by terfenadine. This study indicates that terfenadine, at least partially, interferes with interleukin-4-activated signaling, leading to terfenadine antagonism against the modulatory impact of interleukin-4 on T-cell cytokines.

【 授权许可】

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