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• W2023542419 startingPage "540" @default.
• W2023542419 abstract "CNS injury stimulates the expression of several proinflammatory cytokines and chemokines, some of which including MCP-1 (also known as CCL2), KC (CXCL1), and MIP-2 (CXCL2) act to recruit Gr-1+ leukocytes at lesion sites. While earlier studies have reported that neutrophils and monocytes/macrophages contribute to secondary tissue loss after spinal cord injury (SCI), recent work has shown that depletion of Gr-1+ leukocytes compromised tissue healing and worsened functional recovery. Here, we demonstrate that astrocytes distributed throughout the spinal cord initially contribute to early neuroinflammation by rapidly synthesizing MCP-1, KC, and MIP-2, from 3 up to 12 h post-SCI. Chemokine expression by astrocytes was followed by the infiltration of blood-derived immune cells, such as type I “inflammatory” monocytes and neutrophils, into the lesion site and nearby damaged areas. Interestingly, astrocytes from mice deficient in MyD88 signaling produced significantly less MCP-1 and MIP-2 and were unable to synthesize KC. Analysis of the contribution of MyD88-dependent receptors revealed that the astrocytic expression of MCP-1, KC, and MIP-2 was mediated by the IL-1 receptor (IL-1R1), and not by TLR2 or TLR4. Flow cytometry analysis of cells recovered from the spinal cord of MyD88- and IL-1R1-knockout mice confirmed the presence of significantly fewer type I “inflammatory” monocytes and the almost complete absence of neutrophils at 12 h and 4 days post-SCI. Together, these results indicate that MyD88/IL-1R1 signals regulate the entry of neutrophils and, to a lesser extent, type I “inflammatory” monocytes at sites of SCI." @default.
• W2023542419 created "2016-06-24" @default.
• W2023542419 creator A5007929833 @default.
• W2023542419 creator A5010855720 @default.
• W2023542419 creator A5013325680 @default.
• W2023542419 creator A5048054881 @default.
• W2023542419 date "2010-05-01" @default.
• W2023542419 modified "2023-10-01" @default.
• W2023542419 title "Astrocytes initiate inflammation in the injured mouse spinal cord by promoting the entry of neutrophils and inflammatory monocytes in an IL-1 receptor/MyD88-dependent fashion" @default.
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• W2023542419 doi "https://doi.org/10.1016/j.bbi.2009.11.007" @default.
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