Suppressed pro-inflammatory response of microglia in CX3CR1 knockout mice.

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.