title: MCPIP1 contributes to the inflammatory response of UVB-treated keratinocytes.
abstract: BACKGROUND
  Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1), also known as regnase-1, negatively regulates many cellular processes including the cellular response to inflammatory agents, differentiation, viability, and proliferation. It possesses a PilT N-terminus (PIN) domain that is directly involved in regulating the stability of transcripts and miRNAs by recognizing stem loop structures and degrading them by endonucleolytic cleavage.
  
  
  OBJECTIVE
  We investigated the role of MCPIP1 in the response of human primary keratinocytes to UVB stress.
  
  
  METHODS
  Keratinocytes were treated with UVB, siRNA against MCPIP1, pharmacological inhibitors of signaling pathways, or subjected to control treatments. The mRNA and protein levels of MCPIP1 and MCPIP1-dependent changes gene expression were analyzed by quantitative (Q)-RT-PCRs and Western blots. Secretion of TNFα and IL-8 was determined by ELISA.
  
  
  RESULTS
  UVB treatment of keratinocytes induced upregulation of MCPIP1 at the mRNA level after 4-8h and at the protein level after 8-16h. MCPIP1 abundance depended on NF-κB activity. Using an siRNA strategy, we found that diminished MCPIP1 resulted in an up-regulation of transcripts coding for IL-8, TNFα, COX-2, and BCL-2, as well as an enhanced release of IL-8. Moreover, decreased phosphorylation of NF-κB and p38 signaling pathways were observed in addition to a slight up-regulation of ERK1/2 directly after UVB treatment. Twenty-four hours later, decreased phosphorylation was observed only for NF-κB and p38. Furthermore, in MCPIP1-suppressed cells, the levels of pro-apoptotic Puma, the phosphorylated form of p53 and the abundance of its target p21 as well as the activity of caspase 3 decreased, while the level of cyclin D1 increased.
  
  
  CONCLUSIONS
  MCPIP1 contributes to the UVB response of keratinocytes by altering metabolic and apoptotic processes and the release of inflammatory mediators.
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Bugara
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Konieczny
authors.affiliation: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wolnicka-Glubisz
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fischer
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Skalniak
authors.affiliation: Cell Bank, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Julia
authors.initials: J
authors.lastname: Borowczyk-Michalowska
authors.affiliation: Cell Bank, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Drukala
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: jolanta.jura@uj.edu.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jura
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes / Q000528:radiation effects*; D016328:NF-kappa B / Q000502:physiology; D012260:Ribonucleases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D012260:Ribonucleases; C510646:ZC3H12A protein, human
keywords: Apoptosis; Cell viability; Keratinocytes; MCPIP1; Signaling pathways; UVB