down-regulation of tristetraprolin expression results in enhanced il-12 and mip-2 production and reduced mip-3 synthesis in activated macrophagestristetraprolin表达的下调导致增强il - 12和mip-2生产和减少mip-3激活巨噬细胞的合成.pdfVIP

Hindawi Publishing Corporation Mediators of Inflammation Volume 2006, Article ID 40691, Pages 1–8 DOI 10.1155/MI/2006/40691 Research Communication Down-Regulation of Tristetraprolin Expression Results in Enhanced IL-12 and MIP-2 Production and Reduced MIP-3α Synthesis in Activated Macrophages Ulla Jalonen, Riina Nieminen, Katriina Vuolteenaho, Hannu Kankaanranta, and Eeva Moilanen The Immunopharmacology Research Group, Medical School, University of Tampere, and Tampere University Hospital, Research Unit, 33014 Tampere, Finland Received 10 July 2006; Accepted 25 September 2006 In inflammation, the post-transcriptional regulation of transiently expressed genes provides a potential therapeutic target. Triste- traprolin (TTP) is of the factors regulating decay of cytokine mRNAs. The aim of the present study was to identify cytokines whose expression is regulated by TTP. We established a TTP knock-down cell line by expressing shRNA against TTP (shTTP cell line). A cytokine antibody array was used to measure cytokine production in macrophages exposed to lipopolysaccharide (LPS). Cytokines IL-6, IL-12, TNF-α, and MIP-2 (a homologue to human IL-8) were expressed at higher levels whereas MIP-3α was produced at lower levels in LPS-treated shTTP cells than in control cells suggesting that the expression of these cytokines is regulated by TTP. The present data provide IL-12, MIP-2, and MIP-3α as novel inflammatory cytokine targets for TTP-mediated mRNA decay and stress the role of TTP in the regulation of the inflammatory process. Copyright © 2006 Ulla Jalonen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION