Regulators of G-protein signalling are modulated by bacterial lipopeptides and lipopolysaccharide.
Regulators of G-protein signalling accelerate the GTPase activity of G(alpha) subunits, driving G proteins in their inactive GDP-bound form. This property defines them as GTPase activating proteins. Here the effect of different Toll-like receptor agonists on RGS1 and RGS2 expression in murine bone marrow-derived macrophages and J774 cells was analysed. After stimulation with TLR2/1 or TLR2/6 lipopeptide ligands and the TLR4/MD2 ligand lipopolysaccharide, microarray analyses show only modulation of RGS1 and RGS2 among all the regulators of G-protein signalling tested. Real-time PCR confirmed modulation of RGS1 and RGS2. In contrast to RGS2, which was always downregulated, RGS1 mRNA was upregulated during the first 30 min after stimulation, followed by downregulation. Similar results were also found in the murine macrophage cell line J774. The ligand for intracellular TLR9 modulates RGS1 and RGS2 in a similar manner. However, the TLR3 ligand poly(I:C) permanently upregulates RGS1 and RGS2 expression indicating a different modulation by the MyD88- and TRIF-signalling pathway. This was confirmed using MyD88(-/-) and TRIF(-/-) bone marrow-derived macrophages. Modulation of RGS1 and RGS2 by Toll-like receptor ligands plays an important role during inflammatory and immunological reactions after bacterial and viral infection.
Riekenberg
Sabine
S
Cellular Immunology, Department of Immunology and Cell Biology, Research Center Borstel, Germany.
Farhat
Katja
K
Debarry
Jennifer
J
Heine
Holger
H
Jung
Günther
G
Wiesmüller
Karl-Heinz
KH
Ulmer
Artur J
AJ
D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D055666:Lipopeptides / Q000096:biosynthesis / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019779:Salmonella enterica / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D033942:Adaptor Proteins, Vesicular Transport; D019204:GTP-Binding Proteins; D055666:Lipopeptides; D008070:Lipopolysaccharides; D011070:Poly I-C; D020710:RGS Proteins; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; C488188:Rgs1 protein, mouse; C105345:Rgs2 protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse; C495370:Tlr9 protein, mouse