IL-6-mediated MHC class II induction on RIN-5AH insulinoma cells by IFN-γ occurs via the G-protein pathway

Major histocompatibility complex (MHC) class II antigen expression has been implicated in the pathogenesis of autoimmune type 1 diabetes. In this study we examined the role of various cytoldnes that may induce MHC class II surface antigen expression, using the rat insulinoma line RIN-5AH as a pertinent model system. As in another study, the ability of IFN-γ to amplify MHC class II antigen expression 4-fold is demonstrated. At the same time we noted a 5-fold increase of these histocompatibility antigens by IL-6. Signal transduction analysis reveals that IL-6-induced MHC class II expression is specifically mediated by the G-protein system (activation of p21ras by IL-6) since mevalonic acid lactone (a Gprotein inhibitor) abolishes the action of IL-6. In contrast, IFN-γ, which does not activate p21ras, is not inhibited by protein kinase C (PKC) inhibitors but by those of the G-protein pathway. This finding raises the possibility that IFN-γ induces RIN cells to secrete IL-6 (as shown previously, as well as in this paper) which, in turn, increases class II antigen expression via the G-protein pathway. This action may be unique to IL-6 or in synergy with IFN-γ. Other cytokines such as IL-1α and β, and TNF-α induce a smaller increase in MHC class II antigens on RIN cells, and appear to activate both the G-protein and the PKC signal transduction pathways to varying degrees. Therefore, injury of pancreatic β-cells and possible induction of autoimmune type 1 diabetes via various cytokines may be caused by IL-6 or IFN-γ, or by their ability to induce MHC class II antigen upregulation

From pre-storm activity to magnetic storms: a transition described in terms of fractal dynamics

International audienceWe show that distinct changes in scaling parameters of the Dst index time series occur as an intense magnetic storm approaches, revealing a gradual reduction in complexity. The remarkable acceleration of energy release ? manifested in the increase in susceptibility ? couples to the transition from anti-persistent (negative feedback) to persistent (positive feedback) behavior and indicates that the occurence of an intense magnetic storm is imminent. The main driver of the Dst index, the VBSouth electric field component, does not reveal a similar transition to persistency prior to the storm. This indicates that while the magnetosphere is mostly driven by the solar wind the critical feature of persistency in the magnetosphere is the result of a combination of solar wind and internal magnetospheric activity rather than solar wind variations alone. Our results suggest that the development of an intense magnetic storm can be studied in terms of "intermittent criticality" that is of a more general character than the classical self-organized criticality phenomena, implying the predictability of the magnetosphere

Scaling and a Fokker-Planck model for fluctuations in geomagnetic indices and comparison with solar wind as seen by Wind and ACE

The evolution of magnetospheric indices on temporal scales shorter than that of substorms is characterized by bursty, intermittent events that may arise from turbulence intrinsic to the magnetosphere or that may reflect solar wind-magnetosphere coupling. This leads to a generic problem of distinguishing between the features of the system and those of the driver. We quantify scaling properties of short-term (up to few hours) fluctuations in the geomagnetic indices AL and AU during solar minimum and maximum, along with the parameter that is a measure of the solar wind driver. We find that self-similar statistics provide a good approximation for the observed scaling properties of fluctuations in the geomagnetic indices, regardless of the solar activity level, and in the parameter at solar maximum. This self-similarity persists for fluctuations on timescales at least up to about 1–2 hours. The scaling exponent of AU index fluctuations show dependence on the solar cycle, and the trend follows that found in the scaling of fluctuations in . The values of their corresponding scaling exponents, however, are always distinct. Fluctuations in the AL index are insensitive to the solar cycle, as well as being distinct from those in the parameter. This approximate self-similar scaling leads to a Fokker-Planck model which, we show, captures the probability density function of fluctuations and provides a stochastic dynamical equation (Langevin equation) for time series of the geomagnetic indices