Analysis of the Mechanism Regulating the Stability of Rat Macrophage Inflammatory Protein-2 mRNA in RBL-2H3 Cells

Keiichi Numahata, Tatsuya Komagata, Noriyasu Hirasawa, Koh Ichiro Someya, Yi Qun Xiao, Kazuo Ohuchi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Using rat peritoneal neutrophils, the complete nucleotide sequence of rat macrophage inflammatory protein-2 (MIP-2) mRNA including 5′untranslated region (UTR) and 3′UTR was determined (GenBank Accession number, AB060092). It was found that the MIP-2 mRNA has a 70 bp 5′UTR, a 303 bp coding region and a 728 bp 3′UTR which contains adenylate/uridylate (AU)-rich areas defined as AU-rich elements (AREs). Site-directed mutagenesis studies using the tetracycline-sensitive transactivator protein-expressing rat basophilic leukemia cells (RBL-2H3-TO cells) revealed that MIP-2 mRNA mutants which lack the 3′UTR are more stable than MIP-2-wild-type (wt) mRNA. A MIP-2 mRNA mutant in which some mutations were introduced to the ARE was also stable. The stability of MIP-2 mRNA was low in untreated RBL-2H3-TO cells, but it increased in the antigen-stimulated immunoglobulin E (IgE)-sensitized cells. The antigen-induced MIP-2 mRNA stabilization was counteracted by the highly specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the MAPK/ERK kinase (MEK-1) inhibitor PD98059. These findings indicate that ARE is the cis-element which mediates the rapid decay of MIP-2 mRNA, and the antigen stimulation stabilizes MIP-2 mRNA and the p38 MAPK and p44/42 MAPK pathways are involved in the antigen-induced stabilization of MIP-2 mRNA.

Original languageEnglish
Pages (from-to)976-986
Number of pages11
JournalJournal of Cellular Biochemistry
Volume90
Issue number5
DOIs
Publication statusPublished - 2003 Dec 1

Keywords

  • AU-rich element
  • MIP-2
  • RBL-2H3 cells
  • mRNA stability
  • p38 MAPK
  • p44/42 MAPK

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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