Abstract
Neuronal fractalkine acts via its receptor, CX3CR1, on microglia to regulate neuroinflammation. Conflicting results have been reported in studies employing CX3CR1 deficient (Cx3cr1(-/-)) mice. Here, compared to wild-type, endotoxin-treated neuron-glial Cx3cr1(-/-)cultures produced less TNF-α, nitric oxide and superoxide; however, fractalkine treatment inhibited the release of pro-inflammatory factors in wild-type and BV-2 cell cultures. Furthermore, endotoxin-treated BV-2 cells expressing siRNA against CX3CR1 increased nitric oxide and TNF-α production. We hypothesize that CX3CL1-CX3CR1 signaling is neuroprotective and propose that the reduced production of pro-inflammatory signals in Cx3cr1(-/-)microglia may result from compensatory mechanisms and not be the direct result of CX3CR1 deficiency.