Dynamics of neuron-glia interplay upon exposure to unconjugated bilirubin

作者：Silva Sandra L; Osorio Catarina; Vaz Ana R; Barateiro Andreia; Falcao Ana S; Silva Rui F M; Brites Dora^*

来源：Journal of Neurochemistry, 2011, 117(3): 412-424.

DOI：10.1111/j.1471-4159.2011.07200.x

• astrocyte- and neuron-conditioned media
• inflammatory reaction
• nerve cell death
• neuron-microglia mixed cultures
• phagocytosis
• unconjugated bilirubin

P>Microglia are the main players of the brain immune response. They act as active sensors that rapidly respond to injurious insults by shifting into different activated states. Elevated levels of unconjugated bilirubin (UCB) induce cell death, immunostimulation and oxidative stress in both neurons and astrocytes. We recently reported that microglial phagocytic phenotype precedes the release of pro-inflammatory cytokines upon UCB exposure. We investigated whether and how microglia microenvironment influences the response to UCB. Our findings revealed that conditioned media derived from UCB-treated astrocytes reduce microglial inflammatory reaction and cell death, suggesting an attempt to curtail microglial over activation. Conditioned medium from UCB-challenged neurons, although down-regulating tumor necrosis factor-alpha and interleukin-1 beta promoted the release of interleukin-6 and nitric oxide, the activation of matrix metalloproteinase-9, and cell death, as compared with UCB-direct effects on microglia. Moreover, soluble factors released by UCB-treated neurons intensified the phagocytic properties manifested by microglia under direct exposure to UCB. Results from neuron-microglia mixed cultures incubated with UCB evidenced that sensitized microglia were able to prevent neurite outgrowth impairment and cell death. In conclusion, our data indicate that stressed neurons signal microglial clearance functions, but also overstimulate its inflammatory potential ultimately leading to microglia demise.

• 出版日期2011-5
• 单位河北医科大学