Transendothelial migration (TEM) of Th1 and Th17 cells across the blood-brain barrier (BBB) has a critical role in the development of experimental autoimmune encephalomyelitis (EAE). How cytokines produced by inflammatory Th1 and Th17 cells damage the endothelial BBB and promote transendothelial migration of immune cells into the central nervous system (CNS) during autoimmunity is not understood. We therefore investigated the effect of various cytokines on brain endothelial cells. Among the various cytokines tested, such as Th1 (IFN-γ, IL-1α, IL-1β, TNF-α, IL-12), Th2 (IL-3, IL-4, IL-6 and IL-13), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23, GM-CSF) and Treg-specific cytokines (IL-10 and TGF-β), IFN-γ predominantly showed increased expression of ICAM-1, VCAM-1, MAdCAM-1, H2-K and I-A molecules on brain endothelial cells. Furthermore, IFN-γ induced transendothelial migration of CD4 T cells from the apical (luminal side) to the basal side (abluminal side) of the endothelial monolayer to chemokine CCL21 in a STAT-1-dependent manner. IFN-γ also favored the transcellular route of TEM of CD4 T cells. Multicolor immunofluorescence and confocal microscopic analysis showed that IFN-γ induced relocalization of ICAM-1, PECAM-1, ZO-1 and VE-cadherin in the endothelial cells, which affected the migration of CD4 T cells. These findings reveal that the IFN-γ produced during inflammation could contribute towards disrupting the BBB and promoting TEM of CD4 T cells. Our findings also indicate that strategies that interfere with the activation of CNS endothelial cells may help in controlling neuroinflammation and autoimmunity.

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Natural biotic communities from Kalbadevi Bay were monitored in microcosms (1-l glass flasks) to test the hypothesis that iron released from ilmenite through microbial action contributes to proliferation of phytoplankton. Microcosms containing ilmenite had significantly higher phytoplankton growth compared with controls containing no ilmenite or those containing only ferrous sulfate. Phytoplankton cell numbers in the ilmenite-supplemented treatment were 20= higher than in controls. The later stages were marked by the dominance of bottom dwelling Nitzschia spp. and Navicula spp. Iron-preferring Eunotia spp. and Pinnularia spp. were also encountered. Hence, increased phytoplankton biomass may be attributable to the steady release of bioavailable iron. We therefore infer that ilmenite mineral might sustain the phytoplankton community in ilmenite-dominated systems. Increases in density and diversity of phytoplankton over time and significant interrelationship between various parameters in the microcosm containing ilmenite indicate that stimulatory effect of iron released from this mineral could be beneficial to the biota in the system.