IFN-γ downregulates interleukin-4 functional activity on monocytes by multiple mechanisms
IFN-γ downregulates interleukin-4 functional activity on monocytes by multiple mechanisms
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DOI：
10.1089/107999002753675703
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发表时间：
2002-03-01
影响因子：
2.3
通讯作者：
Hart, PH
中科院分区：
文献类型：
--
作者：
Bonder, CS;Davies, KVL;Hart, PH
白介素4(IL-4)对单核细胞具有很强的抗炎作用，可抑制脂多糖(LPS)诱导的肿瘤坏死因子-α(TNF-α)和IL-1β的产生。干扰素培养通过多种机制改变人单核细胞对IL-4的反应。如先前发表的，干扰素-γ降低了IL-4激活的信号转导和转录激活因子-6(STAT-6)。这与IL-4无法抑制内毒素诱导的肿瘤坏死因子-α的产生有关，但与IL-1β的产生无关。第二种机制是在暴露于干扰素-γ后约48小时，涉及显著抑制细胞表面IL-4受体(IL-4R)的表达，这与对IL-4的额外功能反应的丧失有关，包括IL-4诱导的抑制内毒素诱导的IL-1β的产生。这项研究确认了干扰素-γ对IL-4反应的进一步作用，包括减少人单核细胞表面IL-4R的表达。干扰素-γ处理的单核细胞释放的可溶性γ-干扰素增加，为干扰素-γ控制IL-4的功能活性提供了另一种机制。这项研究进一步表征了1型和2型细胞因子调节系统的相反作用。
Interleukin-4 (IL-4) has potent anti-inflammatory properties on monocytes and suppresses lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta production. Culture with interferon (IFN-gamma) alters human monocyte responses to IL-4 by multiple mechanisms. As previously published, IFN-gamma reduced IL-4-activated signal transducer and activator of transcription-6 (STAT-6). This correlated with an inability of IL-4 to suppress LPS-induced TNF-alpha but not IL-1beta production. A second mechanism, apparent some 48 h after exposure to IFN-gamma, involved a significant suppression of IL-4 receptor (IL-4R) expression at the cell surface, and this correlated with the loss of additional functional responses to IL-4, including IL-4-induced suppression of LPS-induced IL-1beta production. This study identified a further role of IFN-gamma on IL-4 responses, including reduced IL-4R surface expression by human monocytes. Increased release of soluble gammac from IFN-gamma-treated monocytes provides an additional mechanism by which IFN-gamma may control the functional activity of IL-4. This study characterizes further the opposing effects of the type 1 and type 2 cytokine regulatory systems.