Moreover, ERK and mTOR are key components of the intracellular signaling switch that transduce EGFR activation into the aforementioned char acteristic of the activated selleck chemical Perifosine microglia phenotype. The importance of sPLA2 IIA in neurodegenerative diseases, especially in those associated with inflamma tory processes has started to emerge in recent years. Several studies have shown an increase in the expression of sPLA2 IIA in reactive astrocytes both in experimental models of cerebral ischemia and in specific regions of human brains in AD associated with amyloid plaques. It has been suggested that the inter action of astrocytes with AB and other inflammatory stimuli, such as IL 1B or TNF, are responsible for this sPLA2 IIA induction which could Inhibitors,Modulators,Libraries be associated in the early inflammatory events.

Although the ability of sPLA2 IIA to affect the functional activities and the survival or death of astrocytes, neurons and oligoden drocytes has been explored, this is the first study in which the effect of sPLA2 IIA on microglial cells has been addressed. Our interest in microglia owes to the fact that Inhibitors,Modulators,Libraries these cells, in conjunction with astrocytes, are responsible Inhibitors,Modulators,Libraries for coordinating inflammatory responses in the brain and elicit immune responses against patho logical stimuli. Several pro inflammatory and immunoregulatory responses associated with certain secreted PLA2 types have been reported in previous studies. Thus, sPLA2 IIA induces differentiation of monocytes into monocyte derived den dritic cells or alternatively activated macrophages, both human and bee venom type III trigger maturity of dendritic cells, which is accompanied by up regulation of surface markers and by an increase in their migratory and immunostimulatory capacity.

Furthermore, type V regulates phagocytosis on macrophages by modu lating phagosome maturation. sPLA2 IIA also enhances the expression of COX 2 in mast cells and pro motes degranulation and cytokine release in human eosi nophils, Inhibitors,Modulators,Libraries as well as up regulation of certain surface activation markers. In addition, sPLA2 IIA, IB, X and III elicit proliferative signals, in vitro, in several cell types, and type IIA has proven to be protective even against Inhibitors,Modulators,Libraries oxysterol induced apoptosis in oligodendrocytes.

In this study we showed that sPLA2 IIA, as well as type III, IB and V, enhance the proliferative and phago cytic capacity of BV 2 microglia cells to a similar extent as IFN��, one of the cytokines up regulated in the brain in different disorders selleck and a well known inducer of an activated state in microglial cells. Focusing on type IIA actions, two kind of phagocytosis have been evaluated, phagocytosis of inert particles and of apoptotic cells. The ability of microglia to phagocytose inert material and apoptotic cells is critical for the clearance of pathogen cell debris and dead cells under pathological conditions.