Substance P enhances the production of interferon-induced protein of 10 kDa by human keratinocytes in synergy with interferon-γ
Substance P enhances the production of interferon-induced protein of 10 kDa by human keratinocytes in synergy with interferon-γ
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DOI：
10.1046/j.1523-1747.2002.19626.x
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发表时间：
2002-12-01
影响因子：
6.5
通讯作者：
Watanabe, S
中科院分区：
文献类型：
--
作者：
Kanda, N;Watanabe, S
一种神经肽物质P与皮肤炎症有关。干扰素诱导的10kda蛋白（IP-10）化学吸引T辅助1细胞，并且角化细胞产生的干扰素诱导的10kda蛋白在炎症性皮肤病（如牛皮癣）中增强。我们检测了P物质对人角质形成细胞干扰素诱导的10 kDa蛋白产生的体外影响。虽然P物质本身不能诱导干扰素诱导的10 kDa蛋白的产生，但它可以增强干扰素诱导的10 kDa蛋白的分泌、mRNA的表达和次优浓度干扰素诱导的启动子活性。干扰素诱导的10 kDa启动子蛋白上的干扰素刺激反应元件和两个核因子- kappab位点是P物质增强的原因。P物质单独通过两个核因子- kappab位点增强了转录活性和转录因子结合，而通过干扰素刺激反应元件不改变干扰素诱导的转录活性和转录因子结合。P物质对干扰素诱导的10 kDa蛋白生成和核因子κ b激活的影响被神经激肽-1受体拮抗剂、磷脂酶C抑制剂、细胞内Ca2+螯合剂和抗氧化剂抑制。这些结果表明，P物质可能通过角化细胞上的神经激肽1受体与干扰素γ协同作用，诱导核因子κ b活化和干扰素诱导的10 kDa蛋白的产生。P物质的这些作用可能通过磷脂酶C活化、细胞内Ca2+信号和活性氧中间体介导。
A neuropeptide substance P is related to skin inflammation. Interferon-induced protein of 10 kDa (IP-10) chemoattracts T helper 1 cells, and interferon-induced protein of 10 kDa production by keratinocytes is enhanced in inflammatory skin diseases such as psoriasis. We examined the in vitro effects of substance P on interferon-induced protein of 10 kDa production by human keratinocytes. Though substance P alone did not induce interferon-induced protein of 10 kDa production, it enhanced interferon-induced protein of 10 kDa secretion, mRNA expression, and promoter activity induced by suboptimal concentrations of interferon-gamma. Interferon-stimulated response element and two nuclear factor-kappaB sites on interferon-induced protein of 10 kDa promoter were responsible for the enhancement by substance P. Substance P alone enhanced transcriptional activity and transcription factor binding through the two nuclear factor-kappaB sites, whereas it did not alter interferon-gamma-induced transcriptional activity and transcription factor binding through interferon-stimulated response element. The effects of substance P on interferon-induced protein of 10 kDa production and nuclear factor-kappaB activation were inhibited by neurokinin-1 receptor antagonist, phospholipase C inhibitor, intracellular Ca2+ chelator, and anti-oxidant. These results suggest that substance P may induce nuclear factor-kappaB activation and interferon-induced protein of 10 kDa production in synergy with interferon-gamma via neurokinin-1 receptor on keratinocytes. These effects of substance P may be mediated via phospholipase C activation, intra-cellular Ca2+ signal, and reactive oxygen intermediates.