Regulation of Chemokine mRNA Stability by Lipopolysaccharide and IL-10
作者： Roopa Biswas , Shyamasree Datta , Jaydip Das Gupta , Michael Novotny , Julie Tebo
DOI: 10.4049/JIMMUNOL.170.12.6202
关键词: RNA 、 Untranslated region 、 Messenger RNA 、 Chemokine 、 Biology 、 Transcription (biology) 、 Molecular biology 、 Lipopolysaccharide 、 In vitro 、 Proinflammatory cytokine
摘要: IL-10 has been reported to inhibit the expression of LPS-induced proinflammatory cytokines and chemokines by altering rate specific mRNA decay although molecular target(s) for its action remain unknown. In present study, using primary peritoneal exudate macrophages a cell culture model in which tetracycline-responsive promoter controls transcription CXC ligand 1 (KC) mRNA, we demonstrate that LPS promotes time-dependent increase KC stability. Although had no direct effect on decay, this treatment antagonized stabilizing LPS. The mechanisms involved were further explored cell-free degradation system. A 5'-capped, polyadenylated vitro transcript derived from 3'-untranslated region exhibited presence protein extracts prepared untreated RAW264.7 macrophages. Extracts LPS-treated cells reduced activity change was if costimulated with IL-10. substrate AU-rich element motifs mutated minimal did not vary treated or nonadenylated RNA also degraded diminished concert, these findings stability is regulated alterations activities govern both deadenylation body. effects reflect antagonism response
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