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
中科院分区:
文献类型:
--
作者:
Dobosz E;Wilamowski M;Lech M;Bugara B;Jura J;Potempa J;Koziel J
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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