Myeloid-derived suppressor cells (MDSCs) and mechanistic target of rapamycin (mTOR) signaling pathway interact through inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in asthma.

backgroundDown-regulation of mechanistic target of rapamycin (mTOR) activity in myeloid-derived suppressor cells (MDSCs) has been shown to promote inducible nitric oxide (NO) synthase (iNOS) expression and NO production. Importantly, pharmacological inhibition of iNOS blocks MDSCs recruitment in immunological hepatic injury. As bronchial asthma is also an immune disease, whether mTOR could interact with MDSCs via iNOS and NO or not is unclear.

objectiveThe aim of this study was to determine whether mTOR could interact with MDSCs via iNOS and NO in asthma.

methodsOvalbumin-induced asthma mouse model was established to perform our investigation, and asthmatic markers were evaluated by hematoxylin and eosin (H&E), immunohistochemistry (IHC), and periodic acid-Schiff (PAS) staining. The levels of iNOS and NO in serum were determined by enzyme linked immunosorbent assay (ELISA). Mice lung tissues were stained with antibodies against phosphorylated (p)-mTOR, and p-p70S6K, and yellow/brown staining was considered as giving a positive signal, meanwhile, the protein levels of p-mTOR, and p-p70S6K were also detected using western blot assay. Mice iNOS activity was determined by radioimmunoassay.

resultsTumor-derived MDSCs in asthmatic mice were regulated by mTOR and iNOS. mTOR pathway activation in asthmatic mice was regulated by iNOS and tumor-derived MDSCs. NO production in asthmatic mice was regulated by mTOR and tumor-extracted MDSCs. Positive correlation of iNOS with mTOR pathway and serum MDSCs was observed.

conclusionThe data indicated that rapamycin, an inhibitor of mTOR, blocked iNOS and NO production during asthma onset. Thus, our results revealed potential novel targets for asthma therapy.