TGF-beta Increases CX3CR1 Expression and Attenuates Lipopolysaccharide (LPS) Induced Microglia Activation
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. College of Biological Sciences Honors Theses; 2010
Interactions between Fractalkine (CX3CL1) and Fractalkine receptor (CX3CR1) in the CNS function to modulate the activation of microglia. The Godbout Laboratory has recently reported that CX3CR1 is down regulated on microglia after lipopolysaccharide (LPS) injection and that this down-regulation was protracted (24 h)on microglia of aged mice (20 mo) compared to adult mice (3- 6 mo). This extended reduction in receptor expression in aged microglia corresponded with exaggerated Interleukin 1-b expression and an impaired recovery from the behavioral symptoms of sickness. The underlying cause of the protracted down regulation of the Fractalkine receptor on microglia of aged mice is unknown but may be related to an age-related decrease in levels of the thanti-inflammatory cytokine, Transforming growth factor beta (TGFβ). Therefore, the purpose of this study was to determine the extent to which TGFβ is involved in the regulation of CX3CR1 expression on microglia. In this study cultured BV2 microglia were used to determine effects of TGFβ and LPS on CX3CR1 in vitro. Here it is shown that LPS treatment of BV2 cells are caused a reduction in CX3CR1 and increase in Il;-6 in a dose dependent manner.. Moreover, culturing the BV-2 cells with LPS conditioned media was sufficient to cause a reduction in CX3CR but did increase IL-6 secretion. These data indicate that CX3CR1 goes down prior to the microglia being activated. In the next set of studies, TGFβ pretreatments enhanced CX3CR1 expression and attenuated the LPS-induced increase in IL-1β expression. Last, ICV injection of TGFΒ enhanced expression of CX3CR1. Taken together these data support the hypothesis that TGFΒ is important in up regulating CX3CR1 and attenuating microglia activation.
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