Role of Pseudomonas aeruginosa quorum sensing (QS) molecules on the viability and cytokine profile of human mesenchymal stem cells

Pseudomonas aeruginosa infections represent one of the major threats for injured or transplanted lungs and for their healing. Considering that the mesenchymal stem cells (MSCs) are a major tool for the regenerative medicine, including therapy of lung damaging diseases, the aim of this paper was to investigate the effects of P. aeruginosa quorum sensing signaling molecules (QSSMs) on human MSCs death signaling pathways and cytokine profile. Our data revealed that N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), N-butanoyl-L-homoserine lactone (C4-HSL), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), and its precursor, 2-heptyl-4-quinolone (HHQ), significantly impact on several core signaling mechanisms of MSCs in a specific and time-dependent manner. Even if all tested autoinducers interfered with the MSCs apoptotic genes expression, only OdDHL and HHQ significantly promoted MSCs apoptosis, by 14- and 23-fold respectively, this aspect being confirmed by the flow cytometry assay. The tested QSSMs induced a heterogeneous cytokine profile of the treated MSCs. The level of IL-1 was increased by OdDHL, IL-8 production was stimulated by all tested autoinducers, IL-6 was modulated mostly by PQS and IL-10 by HHQ. The significant influence of the purified bacterial autoinducers on the MSCs signaling pathways may suggest that the accumulation of these mediators could interfere with the normal function of these cells in the human body, and eventually, impair or abolish the success of the stem cells therapy during P. aeruginosa infections.