To determine which TLR signal pathway plays the most important role in microglial activation in response to environmental stress that leads to PD pathophysiology, we investigated, in microglia-like BV-2 cells, differential roles of TLR2, TLR4, and TLR9 in inflammatory responses of TNF-α, IL-1β, and iNOS to MPP+ stress and found that TLR4 plays a critical role in the inflammatory responses. This evidence concerns the gene IL1B and Parkinson disease.