title: Suppressed pro-inflammatory response of microglia in CX3CR1 knockout mice.
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.
authors.affiliation: Department of Pathology, Box 359635, 325 9th Ave University of Washington, Seattle, WA 98104, USA.
authors.forename: Hayley A
authors.initials: HA
authors.lastname: Mattison
authors.forename: Hui
authors.initials: H
authors.lastname: Nie
authors.forename: Huiming
authors.initials: H
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Jau-Shyong
authors.initials: JS
authors.lastname: Hong
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000502:physiology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D018836:Inflammation Mediators; D019707:Receptors, Chemokine