Effect of HSP70 and Hydrogen Sulfide Donor on Activation of THP-1 Cells by Various Allergens

Abstract House dust mites (HDM) are a common source of indoor allergens and are involved in the pathogenesis of allergic asthma. Allergens contained in HDM can bind to various pathogen-associated molecular agents, including lipopolysaccharides (LPS) and β-glucans. HDM allergens activate TLR4-dependent macrophage signaling pathways, leading to increased production of reactive oxygen species (ROS) and excessive release of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. The recombinant human heat shock protein HSP70 and the fast hydrogen sulfide donor sodium thiosulfate (STS) were tested for anti-inflammatory effects on intracellular signaling in THP-1 human cells in combination with subsequent addition of a HDM extract and β-glucan. HSP70 and STS were shown to significantly reduce the HDM- and β-glucan-induced production of ROS, TNFα, IL-1β, and IL-6 in THP-1 human promonocyte cells and to decrease the levels of the TLR2 and TLR4 cell receptors. HSP70 and STS were additionally found to restore the glutathione levels in the cells. Cell receptors, intracellular signal transduction pathways, and endocytosis mechanisms were demonstrated to play an important role in the mechanisms whereby STS and exogenous HSP70 protect THP-1 cells from the effects of HDM and β-glucan. Signaling pathways involving p38MAPK, PI3K, and NF-κB were found to play a key role in the protective mechanisms.