PMID- 14624457 OWN - NLM STAT- MEDLINE DCOM- 20040720 LR - 20091119 IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 90 IP - 5 DP - 2003 Dec 1 TI - Analysis of the mechanism regulating the stability of rat macrophage inflammatory protein-2 mRNA in RBL-2H3 cells. PG - 976-86 AB - 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. CI - Copyright 2003 Wiley-Liss, Inc. FAU - Numahata, Keiichi AU - Numahata K AD - Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. FAU - Komagata, Tatsuya AU - Komagata T FAU - Hirasawa, Noriyasu AU - Hirasawa N FAU - Someya, Koh-ichiro AU - Someya K FAU - Xiao, Yi-Qun AU - Xiao YQ FAU - Ohuchi, Kazuo AU - Ohuchi K LA - eng SI - GENBANK/AB060092 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (3' Untranslated Regions) RN - 0 (5' Untranslated Regions) RN - 0 (Chemokine CXCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Monokines) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 1) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - 3' Untranslated Regions/genetics MH - 5' Untranslated Regions/genetics MH - Animals MH - Base Sequence MH - Chemokine CXCL2 MH - Enzyme Inhibitors/pharmacology MH - Leukemia/*genetics/metabolism/pathology MH - MAP Kinase Kinase 1 MH - Male MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - Molecular Sequence Data MH - Monokines/*genetics/metabolism MH - Mutagenesis, Site-Directed MH - Neutrophils/drug effects/enzymology MH - Peritoneum/cytology MH - *RNA Stability MH - RNA, Messenger/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Regulatory Sequences, Nucleic Acid/genetics MH - Signal Transduction MH - Tumor Cells, Cultured MH - p38 Mitogen-Activated Protein Kinases EDAT- 2003/11/19 05:00 MHDA- 2004/07/21 05:00 CRDT- 2003/11/19 05:00 PHST- 2003/11/19 05:00 [pubmed] PHST- 2004/07/21 05:00 [medline] PHST- 2003/11/19 05:00 [entrez] AID - 10.1002/jcb.10710 [doi] PST - ppublish SO - J Cell Biochem. 2003 Dec 1;90(5):976-86. doi: 10.1002/jcb.10710.