Effects of serine protease inhibitor, tame, on IL-1β in LPS-stimulated human monocytes: Relationship between synthesis and release of a 33-kDa precursor and the 17-kDa biologically active species
Effects of serine protease inhibitor, tame, on IL-1β in LPS-stimulated human monocytes: Relationship between synthesis and release of a 33-kDa precursor and the 17-kDa biologically active species
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丝氨酸蛋白酶抑制剂 Tame 对 LPS 刺激的人单核细胞中 IL-1β 的影响：33 kDa 前体和 17 kDa 生物活性物质的合成和释放之间的关系
作者：
J. Jessop;Sylvia L. Henry;T. Hoffman
体外LPS刺激人单核细胞可诱导17-kDa成熟IL-1β（mIL-1β）的释放，但不导致前体IL-1β（pIL-1β）的释放。相比之下，丝氨酸蛋白酶抑制剂Nα-（对甲苯磺酰基）-L-精氨酸甲酯（驯服; 10 mM）存在6或18 h也与LPS刺激的33 kDa pIL-1β释放相关。这些效应最初是从观察结果中发现的，即在存在驯服的情况下，单核细胞释放的总IL-1β产生的部分（通过ELISA检测）增加，免疫印迹试验证实该部分主要是33-kDa IL-1β。在长期（18 h）暴露于驯服后，还观察到单核细胞蛋白质合成的总体降低，并与IL-1β合成的降低（主要影响31 kDa pIL-1β）和TNF-α产生的剂量依赖性抑制相关。乳酸脱氢酶（LDH）释放的平行检测表明pIL-1β的释放与细胞裂解无关。这些结果表明，TAME可降解丝氨酸蛋白酶可能参与33-kDa pIL-1β的原位产生和最终蛋白水解，但可能与IL-1β分子的成熟或IL-1β释放的信号传导无关。IL-1β释放似乎依赖于合成的总IL-1β的量。丝氨酸蛋白水解可能构成过量前体的降解途径，如果受到干扰，可能导致释放更高分子量形式的IL-1β。
LPS stimulation of human monocytes in vitro induced release of the 17-kDa mature IL-1β (mIL-1β) but did not result in release of precursor IL-1β (pIL-1β). In contrast, the presence of a serine protease inhibitor, Nα-(p-toluene sulfonyl)-L-arginine methyl ester (TAME; 10 mM) for 6 or 18 h was associated with the LPS-stimulated release of the 33-kDa pIL-1β as well. These effects were initially discerned from observations that the fraction of the total IL-1β produced (as detected by ELISA) that was released from monocytes increased in the presence of TAME, and immunoblot assays confirmed that this fraction was predominantly 33-kDa IL-1β. A global decrease in monocyte protein synthesis was also observed after prolonged (18-h) exposure to TAME and was associated with a decrease in IL-1β synthesis, predominantly affecting 31-kDa pIL-1β, and a dose-dependent inhibition of TNF-α production. Parallel examination of lactate dehydrogenase (LDH) release indicated thatpIL-1β release was unrelated to cell lysis. These results demonstrate that TAME-inhibitable serine proteases are probably involved in the production and eventual proteolysis of the 33-kDa pIL-1β in situ but are probably not mechanistically related to either maturation of the IL-1β molecule or signaling of IL-1β release. IL-1β release appears to be dependent on the amount of total IL-1β synthesized. Serine proteolysis may constitute a degradative pathway for excess precursor, which, if interfered with, could result in release of the higher-molecular-weight forms of IL-1β.
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DOI：
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发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
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DOI：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
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发表时间：
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Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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