title: MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional Regulation of IL-8 Production.
abstract: 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.
authors: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Ewelina
authors: E
authors: Dobosz
authors: Mateusz
authors: M
authors: Wilamowski
authors: Maciej
authors: M
authors: Lech
authors: Beata
authors: B
authors: Bugara
authors: Jolanta
authors: J
authors: Jura
authors: Jan
authors: J
authors: Potempa
authors: Joanna
authors: J
authors: Koziel
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001424:Bacterial Infections / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D055029:Inverted Repeat Sequences / Q000235:genetics; D022423:Myeloid Cells / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D016209:Interleukin-8; D012333:RNA, Messenger; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human