Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining a modified silver-gold staining was used for discriminating monocytic lineage cells in brain and TEM to deliver ultramicroscopic details of these cells in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Both the MIF and Notch signaling pathways may be promising targets for developing novel therapeutic interventions for uveitis. Our data suggest that the MIF-Notch axis may play an important role in the pathogenesis of EAU. Over-expression of MIF exaggerates ocular inflammation, and this exaggerated inflammation is associated with the activation of the Notch signaling pathway. The expression of both MIF and its receptors are elevated in EAU mice. We demonstrated that over-expression of MIF exaggerated ocular inflammation, which was associated with the activation of the Notch signaling. Further, a MIF antagonist ISO-1 attenuated intraocular inflammation, and inhibited the differentiation of Th1 and Th17 in EAU mice. The Notch inhibitor DAPT reduced the expression of NICD, Hes-1 and proinflammatory cytokines. Compared to injected and untreated EAU mice, the level of proinflammatory cytokines, the expression of Notch1, Notch4, Dll4, NICD and Hes-1 increased, but the ERG a- and b-wave amplitudes decreased in injected EAU mice. We found that expression of MIF and its two receptors CD74 and CD44 was increased in the EAU mouse retina. Retinal function was evaluated with electroretinography (ERG). The levels of proinflammatory cytokines were detected by real-time PCR and ELISA. Three weeks after vectors delivery, EAU was induced with a subcutaneous injection of a mixture of IRBP peptide with CFA. Mutant AAV8 (Y733F)-CBA-MIF or AAV8 (Y733F)-CBA-eGFP vector was delivered subretinally into B10.RIII mice respectively. We examined whether MIF could exaggerate inflammatory response in a mouse model of experimental autoimmune uveitis (EAU) and explored the underlying mechanism.
0 kommentar(er)
