| First Author | Sato A | Year | 2012 |
| Journal | J Neuroinflammation | Volume | 9 |
| Pages | 65 | PubMed ID | 22483094 |
| Mgi Jnum | J:312264 | Mgi Id | MGI:6756574 |
| Doi | 10.1186/1742-2094-9-65 | Citation | Sato A, et al. (2012) Interleukin-1 participates in the classical and alternative activation of microglia/macrophages after spinal cord injury. J Neuroinflammation 9:65 |
| abstractText | BACKGROUND: Microglia and macrophages (MG/MPhi) have a diverse range of functions depending on unique cytokine stimuli, and contribute to neural cell death, repair, and remodeling during central nervous system diseases. While IL-1 has been shown to exacerbate inflammation, it has also been recognized to enhance neuroregeneration. We determined the activating phenotype of MG/MPhi and the impact of IL-1 in an in vivo spinal cord injury (SCI) model of IL-1 knock-out (KO) mice. Moreover, we demonstrated the contribution of IL-1 to both the classical and alternative activation of MG in vitro using an adult MG primary culture. METHODS: SCI was induced by transection of the spinal cord between the T9 and T10 vertebra in wild-type and IL-1 KO mice. Locomotor activity was monitored and lesion size was determined for 14 days. TNFalpha and Ym1 levels were monitored to determine the MG/MPhi activating phenotype. Primary cultures of MG were produced from adult mice, and were exposed to IFNgamma or IL-4 with and without IL-1beta. Moreover, cultures were exposed to IL-4 and/or IL-13 in the presence and absence of IL-1beta. RESULTS: The locomotor activity and lesion area of IL-1 KO mice improved significantly after SCI compared with wild-type mice. TNFalpha production was significantly suppressed in IL-1 KO mice. Also, Ym1, an alternative activating MG/MPhi marker, did not increase in IL-1 KO mice, suggesting that IL-1 contributes to both the classical and alternative activation of MG/MPhi. We treated primary MG cultures with IFNgamma or IL-4 in the presence and absence of IL-1beta. Increased nitric oxide and TNFalpha was present in the culture media and increased inducible NO synthase was detected in cell suspensions following co-treatment with IFNgamma and IL-1beta. Expression of the alternative activation markers Ym1 and arginase-1 was increased after exposure to IL-4 and further increased after co-treatment with IL-4 and IL-1beta. The phenotype was not observed after exposure of cells to IL-13. CONCLUSIONS: We demonstrate here in in vivo experiments that IL-1 suppressed SCI in a process mediated by the reduction of inflammatory responses. Moreover, we suggest that IL-1 participates in both the classical and alternative activation of MG in in vivo and in vitro systems. |
