Terfenadine antagonism against interleukin-4-modulated gene expression of T cell cytokines.
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 [32P]-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.
Maeda
Akira
A
Department of Dermatology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama-shi, Osaka 589-8511, Japan.
Matsushita
Kiyomi
K
Yamazaki
Fumie
F
Kawada
Akira
A
Tezuka
Tadashi
T
Aragane
Yoshinori
Y
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016593:Terfenadine / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018926:Anti-Allergic Agents; D015848:Interleukin-5; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016753:Interleukin-10; D015847:Interleukin-4; D016593:Terfenadine; D006632:Histamine