Abstract # 3098 Cytokine-mediated cell–cell interaction between choroid plexus epithelium and stroma in response to systemic inflammation

Abstract

We reported that the choroid plexus stromal and epithelial cells produce cytokines 4 h after i.p. administration of lipopolysaccharide (LPS). These choroid plexus-derived as well as leptomeningeal-derived cytokines act on receptors expressed by astrocytic processes to stimulate astrocytes to produce other cytokines 24 h after LPS injection, resulting in brain microenvironmental alteration. We hypothesized the presence of choroid plexus cells that produce cytokines to exert the immediate response earlier than 4 h after LPS injection. Mice received LPS or saline i.p. and were fixed with 4% paraformaldehyde 1 and 4 h later. Using frozen sections of the brain containing the choroid plexus, the expression of cytokines, receptors and cell markers were investigated with double immunofluorescence. The results indicated that choroid plexus stromal macrophages expressed IL-1 β 1 h after LPS and some stromal cells expressed IL-1R1 (IL-1 receptor). These stromal cells expressed IL-6, CXCL2 and CCL2 4 h after LPS and the same cells bore CXCR2 (CXCL1/CXCL2 receptor). Furthermore, the choroid plexus epithelial cells expressed CXCL1 and CXCL2 4 h after LPS and bore CXCR2 and IL-6 receptor. Therefore, the signaling using IL-1 β from choroid plexus macrophages and IL-1R1 on choroid plexus stromal cells is the immediate reaction and triggers the cytokine-mediated cell–cell interactions between choroid plexus epithelial and stromal cells. These interactions within the choroid plexus ignite the cytokine responses exerted by brain parenchymal cells.