Regulation of IL-10 secretion after phagocytosis of Mycobacterium tuberculosis by human monocytic cells.
Downregulation of pro-inflammatory events in the immune response to Mycobacterium tuberculosis is critical to prevent host tissue injury. Interleukin (IL-)10 is an important anti-inflammatory cytokine secreted in human tuberculosis but little is known about the control of such IL-10 release. Using an established cellular model, we measured IL-10 secretion after phagocytosis of M. tuberculosis. Phagocytosis of M. tuberculosis but not of inert latex beads by human monocytic (THP-1) cells resulted in IL-10 secretion maximal at 24 h. The magnitude and kinetics of IL-10 secretion were distinct from IL-10 secretion after phagocytosis of yeast-derived zymosan and depended on transcriptional activity and protein synthesis in infected monocytes. IL-10 secretion was decreased in a dose-dependent manner by specific inhibitors of tyrosine kinases, protein kinase (PK) C and PKA. Inhibition of more than one pathway did not result in further synergistic or additive reduction in IL-10 secretion. Finally, specific neutralising antibody directed against IL-10 demonstrated that IL-10 secreted by infected monocytic cells did not block autologous IL-8 secretion.
Shaw
T C
TC
Department of Infectious Diseases, Imperial College of Science, Technology and Medicine, London, UK.
Thomas
L H
LH
Friedland
J S
JS
D002227:Carbazoles; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009281:Naphthalenes / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D016209:Interleukin-8; D009281:Naphthalenes; D011758:Pyrroles; D016753:Interleukin-10; C057416:KT 5720; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C058819:calphostin C