Abstract
BackgroundMicroglial activation and the proinflammatory response are controlled by a complex regulatory network. Among the various candidates, macrophage colony-stimulating factor (M-CSF) is considered an important cytokine. The up-regulation of M-CSF and its receptor CSF-1R has been reported in brain disease, as well as in diabetic complications; however, the mechanism is unclear. An elevated level of glycated albumin (GA) is a characteristic of diabetes; thus, it may be involved in monocyte/macrophage-associated diabetic complications.ResultsThe basal level of expression of M-CSF/CSF-1R was examined in retinal microglial cells in vitro. Immunofluorescence, real-time PCR, immunoprecipitation, and Western blot analyses revealed the up-regulation of CSF-1R in GA-treated microglial cells. We also detected increased expression and release of M-CSF, suggesting that the cytokine is produced by activated microglia via autocrine signaling. Using an enzyme-linked immunosorbent assay, we found that GA affects microglial activation by stimulating the release of tumor necrosis factor-α and interleukin-1β. Furthermore, the neutralization of M-CSF or CSF-1R with antibodies suppressed the proinflammatory response. Conversely, this proinflammatory response was augmented by the administration of M-CSF.ConclusionsWe conclude that GA induces microglial activation via the release of proinflammatory cytokines, which may contribute to the inflammatory pathogenesis of diabetic retinopathy. The increased microglial expression of M-CSF/CSF-1R not only is a response to microglial activation in diabetic retinopathy but also augments the microglial inflammation responsible for the diabetic microenvironment.
Highlights
Microglial activation and the proinflammatory response are controlled by a complex regulatory network
Wang et al [8] reported that glycated albumin (GA) significantly enhanced the production and release of tumor necrosis factor-a (TNF-a) from retinal microglia in vitro, suggesting that GA contributes to microglial inflammation in diabetic retinopathy
Effects of various agents on microglial viability by MTT assay macrophage colony-stimulating factor (M-CSF)-induced microglial proliferation in a dosedependent manner was confirmed, in which the extent of microglial proliferation correlated well with the increase of the viability measured by MTT assay
Summary
Microglial activation and the proinflammatory response are controlled by a complex regulatory network. The resident macrophages of the central nervous system (CNS), is sensitive to minute changes in their microenvironment and is quickly activated Upon activation, they proliferate and become amoeboid phagocytotic cells that produce a variety of proinflammatory cytokines, nitric oxide (NO), and reactive oxygen intermediates [5,6,7]. They proliferate and become amoeboid phagocytotic cells that produce a variety of proinflammatory cytokines, nitric oxide (NO), and reactive oxygen intermediates [5,6,7] These factors are well known to induce neurodegeneration, the precise mechanism is not fully understood. Through the nonenzymatic glycation of free amino groups in proteins by glucose, leads to the formation of labile Schiff base intermediates that undergo Amadori rearrangement, leading to the relatively stable early adducts ketoamine or fructosamine (so-called Amadori products). GA may have important effects on the initiation and progression of diabetic retinopathy
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