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

被引:38
作者
Dobosz, Ewelina [1 ]
Wilamowski, Mateusz [2 ]
Lech, Maciej [3 ]
Bugara, Beata [2 ]
Jura, Jolanta [2 ]
Potempa, Jan [1 ,4 ]
Koziel, Joanna [1 ]
机构
[1] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Microbiol, Ul Gronostajowa 7, PL-30387 Krakow, Poland
[2] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Gen Biochem, Krakow, Poland
[3] Ludwig Maximilians Univ Munchen, Univ Hosp, Med Klin & Poliklin 4, Munich, Germany
[4] Univ Louisville, Sch Dent, Ctr Oral Hlth & Syst Dis, Louisville, KY 40292 USA
关键词
MCPIP-1; Epithelium; Interleukin-8; Innate immunity; Infection; ENDOPLASMIC-RETICULUM STRESS; NF-KAPPA-B; NEGATIVE REGULATOR; IMMUNE-RESPONSES; OXIDATIVE STRESS; PROTEIN; INTERLEUKIN-8; EXPRESSION; CELLS; PHAGOCYTOSIS;
D O I
10.1159/000448038
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pattern recognition receptors are critical for the detection of invading microorganisms. They activate multiple pathways that lead to the induction of proinflammatory 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 the 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 interleukin (IL)-8 transcript and the lifespan of IL-8 was determined by the presence of the stem-loops/hairpin 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. (C) 2016 S. Karger AG, Basel
引用
收藏
页码:564 / 578
页数:15
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