This study used PGD2 agonists for DP1 and DP2 receptors and TxA2 agonist for TP receptor to treat neuronal SH-SY5Y cells with the combination of ramatroban. Cell proliferation, differentiation, and apoptosis were analyzed by cell-based assays, flow cytometry, and Western blotting.

SY5Y cells were treated by DP1, DP2, TxA2 agonists alone to mimic acute SARS-CoV2 infection, then combined with ramatroban to examineits inhibitory effect on neuroinflammation. SY5Y cells were treated under normoxia (20% O2) and hypoxia (4% O2) conditions. 4% O2 partially induced SY5Y cell differentiation into neuronal phenotype. Combinational treatments with DP1 and DP2 agonists and ramatroban decreased cell death more effectively under 4% O2 than those under 20% O2, suggesting that neuron-physiological condition is important for ramatroban anti-inflammatory activity. This was not observed in combinational treatment with TP agonist and ramatroban, suggesting different responses of PG receptors to ramatroban. ERK2 was found most sensitive to inhibition by ramatroban, while ERK1 and AKT were less responsive, thereby identifying one mechanism of ramatroban on neuronal cell inflammation.