In addition, our data suggest a complex, not linear, signaling network involving these two cascades, as the inhibition of any of those pathways prevents sPLA2 IIA promoted activation of BV 2 microglia cells. It has been described that both pathways cross talk extensively and may regulate each other both positively and nega tively. mTOR selleck can be considered a key node of these complex signaling cascades, and exists as two different entities, the raptor mTOR complex and the rictor mTOR complex. Thus, it has been reported that phosporylation of P70S6K and its substrate, rS6, can take place in a rapamycin dependent manner, or inde pendently of mTOR, being Akt, ERK and even phospha tidic acid, direct upstream effector molecules.

Moreover, inhibition of the raptor mTOR complex can trigger activation of the ERK MAPK cascade, while inhibition of the rictor mTOR complex inhibits Inhibitors,Modulators,Libraries Akt and ERK phosphorylation. We have found that rapamy cin, as well as PD98059, Inhibitors,Modulators,Libraries at concentrations that diminish or even suppress the proliferative and fagocytic capabil ities of sPLA2 IIA activated BV 2 cells, also suppress phosphorylation of ERK, P70S6K and rS6. In this study there was no attempt to investigate more deeply the effect of sPLA2 IIA on the sequential activation Inhibitors,Modulators,Libraries of these signaling proteins or the cross talk between the raptor mTOR rictor mTOR complexes. However, the relation ship between these signaling pathways certainly deserves further, independent study due to the complex link exist ing between their components.

Conclusions In conclusion, our results reveal that sPLA2 IIA activates primary and immortalized BV 2 microglia cells, EGFR plays a key role as a critical regulator of this Inhibitors,Modulators,Libraries sPLA2 IIA mediated effect, and also indicates that shedding of pro HB EGF is a crucial step in this response. Accordingly, the possibility that sPLA2 IIA may affect immune system function in the CNS in certain pathologies should Inhibitors,Modulators,Libraries be carefully considered. Background Microglial cells are considered as central nervous system resident professional macrophages. They con stantly survey the brain parenchyma and react immedi ately to changes in the microenvironment, becoming readily activated inhibitor DAPT secretase in response to infection or injury. They may play a dual role, participating in host defense of the brain and tissue repair, as well as acting as phago cytes to engulf tissue debris and dead cells. However, microglia can also contribute to the establishment or exacerbation of tissue damage depending on the type or intensity of the harmful stimulus. Cerebral ischemia and other neurodegenerative disor ders such as Alzheimers disease, Parkinsons disease, and multiple sclerosis, among others, are asso ciated with proliferation and activation of microglia.