title: Toll-like receptor 2 stimulation decreases IFN-gamma receptor expression in mouse RAW264.7 macrophages.
abstract: Interferon-gamma (IFN-gamma) is a key cytokine in the immune defense against mycobacteria. IFN-gamma activates macrophages to resist the growth of mycobacteria and induces expression of MHC class II molecules required for antigen presentation. Macrophages infected with mycobacteria or stimulated by the interaction of mycobacterial products with toll-like receptor 2 (TLR2) have reduced responses to IFN-gamma. Previous research has shown that infection of mouse macrophages with Mycobacterium avium causes decreased expression of the IFN-gamma receptor (IFNGR). In the present study, we show that TLR2 stimulation of RAW264.7 macrophages with a synthetic lipoprotein, Pam3CSK4, also causes rapid decrease in expression of IFNGR-1 protein, with little change in IFNGR-2 protein levels. The decrease in IFNGR-2 expression in TLR2-stimulated cells required receptor internalization and proteasomal degradation. The level of IFNGR-1 mRNA also decreased in TLR2-stimulated RAW264.7 cells and M. avium-infected cells. The decrease in IFNGR-1 mRNA was shown to be due to decreased transcription. In spite of the decrease in IFNGR-2 receptor expression, activation of Stat1 activation by an optimal dose of IFN-gamma was identical between control and TLR2-stimulated RAW264.7 cells. However, at low suboptimal doses of IFN-gamma, Stat1 activation was decreased in TLR2-stimulated cells.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Curry
authors.forename: Gail R
authors.initials: GR
authors.lastname: Alvarez
authors.forename: Bruces S
authors.initials: BS
authors.lastname: Zwilling
authors.forename: William P
authors.initials: WP
authors.lastname: Lafuse
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000502:physiology*; D051379:Mice; D009162:Mycobacterium avium / Q000276:immunology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D061988:Proteasome Inhibitors; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000502:physiology*; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C494080:Stat1 protein, mouse; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine