IL-1beta augments TNF-alpha-mediated inflammatory responses from lung epithelial cells.
IL-1beta augments TNF-alpha-mediated inflammatory responses from lung epithelial cells.
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DOI：
10.1089/jir.2008.0076
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Finkelstein J
中科院分区：
文献类型：
--
作者：
Saperstein S;Chen L;Oakes D;Pryhuber G;Finkelstein J
白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α（TNF-α）介导了许多炎症性肺部疾病的发生发展。由于IL-1β通常在产生TNF-α的情况下被激活，因此假设IL-1β通过改变TNF受体脱落和表面丰度来改变TNF-α诱导的促炎性上皮细胞功能。在这项研究中，研究了IL-1β对小鼠肺上皮细胞（MLE-15）TNF-α介导的趋化因子产生以及TNF受体表面表达和脱落的影响。白细胞介素-1 β快速并持续地增强可溶性和表面TNFR 2。这些作用依赖于TNFR 1的表达。TNFR 2小干扰RNA（siRNA）改变了IL-1β反应，显著增加了表面和脱落TNFR 1，这意味着IL-1β根据细胞受体组成选择性地修饰TNF受体。IL-1β或与TNF-α联合给药24 h后，两种受体的mRNA表达均未发生变化，表明效应为转录后效应。IL-1β预处理可增强TNF-α诱导的巨噬细胞炎症蛋白（MIP-2）和KC mRNA表达，同时增加MIP-2和KC蛋白水平。利用针对TNF受体的siRNA和TNFR 1中和抗体的实验证明TNF-α通过TNFR 1诱导MIP-2，而两种受体都可能有助于KC的产生。这些数据表明IL-1β通过增强上皮细胞TNF受体表面表达来调节TNF-α介导的炎性肺病。
Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mediate the development of numerous inflammatory lung diseases. Since IL-1β is typically activated in situations where TNF-α is produced, it was hypothesized that IL-1β alters TNF-α-induced proinflammatory epithelial cell function by altering TNF receptor shedding and surface abundance. In this study, the impact of IL-1β on TNF-α-mediated chemokine production as well as TNF receptor surface expression and shedding were investigated from mouse pulmonary epithelial cells (MLE-15). Interleukin-1β rapidly and persistently enhanced soluble and surface TNFR2. These effects were dependent on TNFR1 expression. TNFR2 small-interfering RNA (siRNA) shifted IL-1β responses, significantly increasing surface and shed TNFR1 implying IL-1β selectively modifies TNF receptors depending on cellular receptor composition. mRNA expression of both receptors was unaltered by IL-1β up to 24 h or in combination with TNF-α indicating effects were post- transcriptional. Interleukin-1β pretreatment enhanced TNF-α-induced macrophage inflammatory protein (MIP)-2 and KC mRNA expression as well as MIP-2 and KC protein levels at the same time point analyzed. Experiments utilizing siRNA against the TNF receptors and a TNFR1 neutralizing antibody demonstrated TNF-α induced MIP-2 through TNFR1 whereas both receptors may have contributed to KC production. These data suggest IL-1β modulates TNF-α–mediated inflammatory lung diseases by enhancing epithelial cell TNF receptor surface expression.
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影响因子：
11.4
作者：
BARBARA, JAJ;SMITH, WB;LOPEZ, AF
通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.3
作者：
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通讯作者：
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DOI：
10.1152/ajplung.1998.275.6.l1110
发表时间：
1998-12-01
影响因子：
4.9
作者：
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通讯作者：
Finkelstein, JN