MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional Regulation of IL-8 Production.

MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional Regulation of IL-8 Production.
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DOI:
10.1159/000448038
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发表时间:
2016
影响因子:
5.3
通讯作者:
Koziel J
Koziel J
中科院分区:
医学2区
文献类型:
--
作者:
Dobosz E;Wilamowski M;Lech M;Bugara B;Jura J;Potempa J;Koziel J

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模式识别受体是检测入侵微生物的关键。它们激活多种途径,导致诱导促炎反应和病原体清除。这种免疫反应的强度和持续时间必须在每个组织中由不同的负调节因子在空间和时间上严格控制。我们假设单核细胞趋化蛋白-1诱导蛋白-1 (MCPIP-1)可能在生理条件和细菌感染下维持上皮免疫稳态中发挥作用。为此,我们检测了MCPIP-1转录本和蛋白在不同组织中的分布。上皮细胞的MCPIP-1蛋白水平高于髓系细胞。MCPIP-1对IL-8转录物发挥RNase活性,IL-8的寿命由IL-8 mRNA 3 ' UTR区域的茎环/发夹(SL)结构的存在决定。此外,利用完全活性的纯化重组MCPIP-1蛋白,我们阐明了MCPIP-1控制IL-8 mRNA水平的机制。总之,我们发现了一种新的依赖il -8的MCPIP-1维持上皮稳态的机制。这项研究首次揭示了MCPIP-1不仅在髓细胞中,而且在上皮细胞中起着至关重要的抗炎作用。
Pattern recognition receptors are critical for the detection of invading microorganisms. They activate multiple pathways that lead to the induction of pro-inflammatory responses and pathogen clearance. The intensity and duration of this immune reaction must be tightly controlled spatially and temporally in every tissue by different negative regulators. We hypothesized that monocyte chemoattractant protein-1–induced protein-1 (MCPIP-1) might play a role in maintaining immune homeostasis in the epithelium both under physiological conditions and upon bacterial infection. To this end, we examined the distribution of MCPIP-1 transcript and protein in various tissues. The MCPIP-1 protein level was higher in epithelial cells than in myeloid cells. MCPIP-1 exerted RNase activity towards the IL-8 transcript and the life-span of IL-8 was determined by the presence of the stem-loops/hairpin (SL) structures at the 3′ UTR region of IL-8 mRNA. Moreover, using fully active, purified recombinant MCPIP-1 protein, we elucidated the mechanism by which MCPIP-1 controls the IL-8 mRNA level. In conclusion, we uncovered a novel IL-8–dependent mechanism via which MCPIP-1 maintains epithelial homeostasis. This study reveals for the first time that MCPIP-1 plays a crucial anti-inflammatory role not only in myeloid cells but also in epithelial cells.
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