The Influence of Toll-like Receptor (TLR-) Agonists on Lysozyme Activity and TNFα-Secretion in THP-1 cells

TLRs (Toll-like receptors) are part of the innate immune system and play a major role in the recognition of pathogens. They participate in the stimulation of monocytes and macrophages by activation of NF-κB and C/EBPβ, two transcription factors that are implicated in lysozyme and TNF-alpha expression. Aim of this study was to investigate the influence of TLR-agonists and other natural compounds on cytokine secretion and lysozyme activity in a comparative assay. To explore the importance of differentiation THP-1 cells were pre-treated with PMA and IFNy. Stimulation of undifferentiated cells with natural products including various bacterial antigens, diterpenes and alkamides had almost no effect on TNF-alpha secretion and lysozyme activity whereas secretion of IL-6 and IL-10 as well as intercellular adhesion was clearly affected. Differentiated THP-1 cells were much more sensitive to further stimulation yet revealed an opposing effect on lysozyme activity and TNF-alpha secretion. The results suggest a coordinated activation of intercellular adhesion and cytokine production in the differentiation process from monocytes to macrophages and highlights the role of natural products as putative immunmodulatory agents.