Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils.

摘要: Ceramides are mediators of inflammatory processes. In experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis (MS), we observed that CerS6 mRNA expression was upregulated 15-fold in peripheral blood leukocytes before the onset EAE symptoms. from MS patients, a 3.9-fold upregulation found. Total genetic deletion and selective leucocytes exacerbated progression clinical symptoms mice. This associated with enhanced leukocyte, predominantly neutrophil infiltration demyelination lumbar spinal cord Interferon-gamma/tumor necrosis factor alpha (IFN-γ/TNF-α) granulocyte colony-stimulating (G-CSF) both drive development induce integrin CD11b chemokine receptor C-X-C motif 2 (CXCR2), found they also expression. vivo, activation/migration neutrophils, as reflected by CXCR2. vitro, activation status IFN-γ/TNF-α-stimulated shown increased nitric oxide adhesion capacity. G-CSF-stimulated migration enhanced, elevated level CXCR2 These data suggest CerS6/C16-Cer mediates feedback regulation inhibiting formation CXCR2, which induced either IFN-γ/TNF-α or G-CSF, respectively. We conclude anti-inflammatory effects during possibly suppressing deactivation neutrophils.