The function of these chemokines on neuronal cells is controversial. While CX3CL1 showed a neuroprotective effect, CCL2 and CXCL1 were reported to be detrimental or protective on neuronal cells. Thus, the pos sible significance of ET induced astrocytic chemokine production would www.selleckchem.com/products/Enzastaurin.html be difficult to discuss in view of the function of neurons and vascular endothelial cells. Inhibitors,Modulators,Libraries On the other hand, the action of CX3CL1 opposes that of CCL2 and CXCL1 in the regulation of microglial function. CCL2 and CXCL1 caused the activation of cul tured microglia and stimulated the production of proinflammatory molecules. Inhibition of CCL2 signals attenuated microglial activation and pro inflammatory cytokine production in animal models of brain injury.
Pro inflammatory cytokine produc tion and migration in cultured microglia were stimulated by CXCL8 IL 8, a human homologue of rat CXCL1. In contrast, CX3CL1 attenuated microglial acti vation Inhibitors,Modulators,Libraries and proinflammatory cytokine production in vitro and in vivo. Mice lacking CX3CL1 receptors Inhibitors,Modulators,Libraries showed enhanced activation of microglia in response to lipopolysaccharide, indicating a repressive role Inhibitors,Modulators,Libraries of CX3CL1 in microglial function. Considering the differ ent actions among CCL2, CXCL1 and CX3CL1 on microglia, the reciprocal regulation of astrocytic chemokine production by ETs may have a pathophysio logical significance in the induction of activated micro glia. Induction of activated microglia promotes the neuroinflammatory response and results in the aggrava tion of neuronal degradation.
Thus, the increase in ETs after brain insults and neurodegenerative diseases Inhibitors,Modulators,Libraries may show a detrimental action on the damaged brain through microglial activation induced by Vandetanib VEGFR inhibitor altered astro cytic chemokine production. Conclusions In this study, activation of ETB receptors altered the pro duction of CCL2, CXCL1 and CX3CL1 in cultured as trocytes. Because astrocytes are a main source of brain chemokines in neurological disorders, alterations of astrocytic chemokine production affect several responses of the damaged brain. Thus, ET induced alterations of astrocytic chemokine production indicate a pathophysio logical significance of astrocytic ETB receptors. Introduction Microglia are increasingly implicated in the pathogenesis of numerous neurodegenerative disorders including Parkinsons, Alzheimers, and lateral sclerosis. The evidence for a microglial component in the development of dementia is particularly convincing in HIV AIDS pa tients, as the primary site of CNS infection is within resident microglia cells. Once infected, activated microglia release a number of pro inflammatory media tors that directly damage nearby neurons, and deregulate normal brain parenchymal homeostasis through their interaction with astrocytes and uninfected microglia.