TNFα-induced long pentraxin PTX3 expression in human lung epithelial cells via JNK
TNFα-induced long pentraxin PTX3 expression in human lung epithelial cells via JNK
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DOI：
10.4049/jimmunol.175.12.8303
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Liu, MY
中科院分区：
文献类型：
--
作者：
Han, B;Mura, M;Liu, MY
长正五聚蛋白3（PTX 3）是一种急性时相蛋白，是新近阐明的天然免疫和炎症介质。作为可溶性模式识别受体，它在抗真菌感染中具有重要作用。PTX 3的过度表达可导致急性肺损伤。肺上皮是防御肺部病原体的关键因素;它还参与与组织损伤相关的急性炎症反应。然而，关于PTX 3在肺上皮中的调节方式知之甚少。在这项研究中，我们发现，静脉注射LPS诱导大鼠肺泡上皮细胞的PTX 3的表达。使用人肺细胞系和原代上皮细胞，我们发现TNF-α以时间和剂量依赖性方式显著上调PTX 3表达，但LPS不上调。放线菌素D或放线菌酮预处理废除TNF-α诱导的PTX 3表达，表明转录和翻译调控的要求。TNF-α诱导的PTX 3表达被JNK特异性抑制剂SP 600125阻断，但不被NF-κ B、ERK或p38 MAPK抑制剂阻断。用小干扰RNA敲低JNK 1或JNK 2也显著降低了调节的PTX 3表达。因此，肺上皮细胞似乎是PTX 3产生的主要局部来源，其可以通过LPS或其他炎性刺激物从这些细胞体内诱导，并且可能是宿主防御和组织损伤的重要介质。JNK通路对调节PTX 3表达的重要性可能是其在肺中调节的潜在靶点。
Long pentraxin 3 (PTX3), an acute-phase protein, is a newly clarified mediator for innate immunity and inflammation. As a soluble pattern recognition receptor., it has a nonredundant role in antifungal infection. Overexpression of PTX3 worsens acute lung injury. The lung epithelium is a critical factor in defense against pulmonary pathogens; it is also involved in acute inflammatory responses related to tissue injury. However, very little is known about how PTX3 is regulated in the lung epithelium. In this study, we found that i.v. injection of LPS induced PTX3 expression in rat lung alveolar epithelium. Using human lung cell lines and primary epithelial cells, we found that PTX3 expression was significantly up-regulated by TNF-alpha in a time- and dose-dependent manner, but not by LPS. Pretreatment with either actinomycin D or cycloheximide abolished TNF-alpha-induced PTX3 expression, indicating the requirement for both transcriptional and translational regulation. The TNF-alpha-induced PTX3 expression was blocked by SP600125, a JNK-specific inhibitor, but not by the inhibitors against NF-kappa B, ERKs, or p38 MAPK. Knockdown of either JNK1 or JNK2 with small interfering RNA also significantly reduced the regulated PTX3 expression. Thus, lung epithelial cells appear to be a major local source for PTX3 production, which could be induced in vivo from these cells by LPS or other inflammatory stimuli, and may be an important mediator for host defense and tissue damage. The importance of the JNK pathway for the regulated PTX3 expression may be a potential target for its regulation in the lung.