LPS Induces the Degradation of Programmed Cell Death Protein 4 (PDCD4) to Release Twist2, Activating c-Maf Transcription to Promote Interleukin-10 Production
Copyright policy )LPS Induces the Degradation of Programmed Cell Death Protein 4 (PDCD4) to Release Twist2, Activating c-Maf Transcription to Promote Interleukin-10 Production
Programmed cell death protein 4 (PDCD4) is a tumor suppressor and has also been shown to suppress production of the immunomodulatory cytokine IL-10. The precise role of PDCD4 in IL-10 induction in macrophages is still not fully understood. Incubation of macrophages with inhibitors of PI3K and mTOR blocked LPS-stimulated PDCD4 degradation and expression of c-Maf and IL-10 production. PDCD4 and the transcription factor Twist2 were shown to form a complex in untreated cells. LPS disrupted the complex allowing Twist2 to bind to the c-Maf promoter. PI3K and mTOR inhibitors prevented this disruption by stabilizing PDCD4 and thereby decreased Twist2 binding to the c-Maf promoter and induction of c-Maf mRNA. These results indicate a regulatory role for PDCD4 and Twist2 in LPS-induced IL-10 production in macrophages. LPS promotes PDCD4 degradation via a pathway involving PI3K and mTOR, releasing Twist2, which induces IL-10 via c-Maf.
- University of Pennsylvania United States
- Trinity College Dublin Ireland
Lipopolysaccharides, Transcription, Genetic, Il-10, Macrophages, TOR Serine-Threonine Kinases, Twist-Related Protein 1, RNA-Binding Proteins, Apoptosis, Cell Line, Interleukin-10, Repressor Proteins, Phosphatidylinositol 3-Kinases, Gene Expression Regulation, Proto-Oncogene Proteins c-maf, Proteolysis, Humans, Apoptosis Regulatory Proteins, Promoter Regions, Genetic
Lipopolysaccharides, Transcription, Genetic, Il-10, Macrophages, TOR Serine-Threonine Kinases, Twist-Related Protein 1, RNA-Binding Proteins, Apoptosis, Cell Line, Interleukin-10, Repressor Proteins, Phosphatidylinositol 3-Kinases, Gene Expression Regulation, Proto-Oncogene Proteins c-maf, Proteolysis, Humans, Apoptosis Regulatory Proteins, Promoter Regions, Genetic
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